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Q02750

- MP2K1_HUMAN

UniProt

Q02750 - MP2K1_HUMAN

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Protein

Dual specificity mitogen-activated protein kinase kinase 1

Gene

MAP2K1

Organism
Homo sapiens (Human)
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 (By similarity). Many inhibitors have been identified including pyrrole derivatives, TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei8 – 92Cleavage; by anthrax lethal factor
Binding sitei77 – 771Inhibitor; via carbonyl oxygen8 Publications
Binding sitei78 – 781Inhibitor; via amide nitrogen and carbonyl oxygen8 Publications
Binding sitei97 – 971ATP6 PublicationsPROSITE-ProRule annotation
Binding sitei97 – 971Inhibitor8 Publications
Active sitei190 – 1901Proton acceptorPROSITE-ProRule annotation
Binding sitei190 – 1901Inhibitor8 Publications
Binding sitei194 – 1941Inhibitor; via carbonyl oxygen8 Publications
Binding sitei208 – 2081ATP6 PublicationsPROSITE-ProRule annotation
Binding sitei208 – 2081Inhibitor8 Publications
Binding sitei212 – 2121Inhibitor; via amide nitrogen8 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi74 – 829ATP6 PublicationsPROSITE-ProRule annotation
Nucleotide bindingi143 – 1464ATP6 PublicationsPROSITE-ProRule annotation
Nucleotide bindingi150 – 1534ATP6 PublicationsPROSITE-ProRule annotation
Nucleotide bindingi192 – 1954ATP6 PublicationsPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase kinase activity Source: UniProtKB
  3. protein kinase activity Source: ProtInc
  4. protein serine/threonine/tyrosine kinase activity Source: UniProtKB
  5. protein serine/threonine kinase activator activity Source: UniProtKB
  6. protein serine/threonine kinase activity Source: Reactome
  7. protein tyrosine kinase activity Source: UniProtKB-KW
  8. receptor signaling protein tyrosine phosphatase activity Source: Ensembl

GO - Biological processi

  1. activation of MAPK activity Source: UniProtKB
  2. activation of MAPKK activity Source: Reactome
  3. axon guidance Source: Reactome
  4. cell cycle arrest Source: BHF-UCL
  5. cell motility Source: Ensembl
  6. cell proliferation Source: Ensembl
  7. cellular component movement Source: ProtInc
  8. cellular senescence Source: BHF-UCL
  9. chemotaxis Source: ProtInc
  10. epidermal growth factor receptor signaling pathway Source: Reactome
  11. Fc-epsilon receptor signaling pathway Source: Reactome
  12. fibroblast growth factor receptor signaling pathway Source: Reactome
  13. Golgi inheritance Source: Ensembl
  14. innate immune response Source: Reactome
  15. insulin receptor signaling pathway Source: Reactome
  16. keratinocyte differentiation Source: Ensembl
  17. labyrinthine layer development Source: Ensembl
  18. MAPK cascade Source: Reactome
  19. melanosome transport Source: Ensembl
  20. mitotic nuclear division Source: Ensembl
  21. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  22. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  23. negative regulation of cell proliferation Source: BHF-UCL
  24. negative regulation of homotypic cell-cell adhesion Source: Ensembl
  25. neurotrophin TRK receptor signaling pathway Source: Reactome
  26. placenta blood vessel development Source: Ensembl
  27. positive regulation of cell differentiation Source: Ensembl
  28. positive regulation of cell migration Source: Ensembl
  29. positive regulation of gene expression Source: UniProt
  30. positive regulation of protein serine/threonine kinase activity Source: UniProtKB
  31. positive regulation of Ras GTPase activity Source: Ensembl
  32. positive regulation of Ras protein signal transduction Source: Ensembl
  33. positive regulation of transcription elongation from RNA polymerase II promoter Source: Ensembl
  34. protein heterooligomerization Source: Ensembl
  35. Ras protein signal transduction Source: Reactome
  36. regulation of early endosome to late endosome transport Source: UniProtKB
  37. regulation of Golgi inheritance Source: UniProtKB
  38. regulation of stress-activated MAPK cascade Source: UniProtKB
  39. regulation of vascular smooth muscle contraction Source: Ensembl
  40. response to axon injury Source: Ensembl
  41. response to glucocorticoid Source: Ensembl
  42. response to oxidative stress Source: Ensembl
  43. signal transduction Source: ProtInc
  44. small GTPase mediated signal transduction Source: Reactome
  45. stress-activated MAPK cascade Source: Reactome
  46. toll-like receptor 10 signaling pathway Source: Reactome
  47. toll-like receptor 2 signaling pathway Source: Reactome
  48. toll-like receptor 3 signaling pathway Source: Reactome
  49. toll-like receptor 4 signaling pathway Source: Reactome
  50. toll-like receptor 5 signaling pathway Source: Reactome
  51. toll-like receptor 9 signaling pathway Source: Reactome
  52. toll-like receptor signaling pathway Source: Reactome
  53. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  54. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  55. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  56. vesicle transport along microtubule Source: Ensembl
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. 2681.
ReactomeiREACT_1391. ERK1 activation.
REACT_22272. Signal transduction by L1.
REACT_22442. Interleukin-1 signaling.
REACT_228255. Uptake and function of anthrax toxins.
REACT_614. RAF phosphorylates MEK.
REACT_9470. Signaling by FGFR.
REACT_962. MEK activation.
SignaLinkiQ02750.

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
Short name:
MKK1
Alternative name(s):
ERK activator kinase 1
MAPK/ERK kinase 1
Short name:
MEK 1
Gene namesi
Name:MAP2K1
Synonyms:MEK1, PRKMK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:6840. 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. cell cortex Source: Ensembl
  2. cytoplasm Source: HPA
  3. cytoskeleton Source: UniProtKB-KW
  4. cytosol Source: UniProtKB
  5. dendrite cytoplasm Source: Ensembl
  6. early endosome Source: UniProtKB
  7. extracellular vesicular exosome Source: UniProt
  8. focal adhesion Source: UniProtKB
  9. Golgi apparatus Source: UniProtKB
  10. late endosome Source: UniProtKB
  11. mitochondrion Source: UniProtKB
  12. nucleus Source: UniProtKB
  13. perikaryon Source: Ensembl
  14. perinuclear region of cytoplasm Source: Ensembl
  15. plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: A 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. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti53 – 531F → S in CFC3. 1 Publication
VAR_035093
Natural varianti128 – 1281G → V in CFC3. 1 Publication
VAR_069780
Natural varianti130 – 1301Y → C in CFC3. 1 Publication
VAR_035094

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi97 – 971K → R: Inactivation. 1 Publication
Mutagenesisi150 – 1501S → A: No loss of activity. 1 Publication
Mutagenesisi212 – 2121S → A: No loss of activity. 1 Publication
Mutagenesisi218 – 2181S → A: Inactivation. 1 Publication
Mutagenesisi222 – 2221S → A: Inactivation. 1 Publication

Keywords - Diseasei

Cardiomyopathy, Disease mutation, Ectodermal dysplasia, Mental retardation

Organism-specific databases

MIMi615279. phenotype.
Orphaneti1340. Cardiofaciocutaneous syndrome.
PharmGKBiPA30584.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 393392Dual specificity mitogen-activated protein kinase kinase 1PRO_0000086365Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei218 – 2181Phosphoserine; by RAF1 Publication
Modified residuei222 – 2221Phosphoserine; by RAF1 Publication
Modified residuei286 – 2861Phosphothreonine1 Publication
Modified residuei292 – 2921Phosphothreonine; by MAPK1By similarity
Modified residuei298 – 2981Phosphoserine; by PAK1 Publication

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
Acetylation by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ02750.
PaxDbiQ02750.
PeptideAtlasiQ02750.
PRIDEiQ02750.

PTM databases

PhosphoSiteiQ02750.

Miscellaneous databases

PMAP-CutDBQ02750.

Expressioni

Tissue specificityi

Widely expressed, with extremely low levels in brain.1 Publication

Gene expression databases

BgeeiQ02750.
CleanExiHS_MAP2K1.
ExpressionAtlasiQ02750. baseline and differential.
GenevestigatoriQ02750.

Organism-specific databases

HPAiCAB003834.
HPA026430.

Interactioni

Subunit structurei

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 ARBB2, LAMTOR3, MAPK1/ERK2, MORG1 and RAF1 (By similarity). Interacts with PPARG and with isoform 1 of VRK2. Interacts with Yersinia yopJ. Interacts with SGK1. Interacts with BIRC6/bruce.By similarity13 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BIRC6Q9NR092EBI-492564,EBI-1765160
BTRCQ9Y2973EBI-492564,EBI-307461
CFLARO15519-13EBI-492564,EBI-4567563
MAPK1P284822EBI-492564,EBI-959949
MAPK3P273612EBI-492564,EBI-73995
RAF1P040495EBI-492564,EBI-365996
VRK2Q86Y072EBI-492564,EBI-1207615
VRK2Q86Y07-12EBI-492564,EBI-1207633
YAP1P469373EBI-492564,EBI-1044059

Protein-protein interaction databases

BioGridi111590. 47 interactions.
DIPiDIP-201N.
IntActiQ02750. 27 interactions.
MINTiMINT-99632.
STRINGi9606.ENSP00000302486.

Structurei

Secondary structure

1
393
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi44 – 5815Combined sources
Helixi65 – 673Combined sources
Beta strandi68 – 769Combined sources
Beta strandi81 – 877Combined sources
Turni88 – 903Combined sources
Beta strandi93 – 1008Combined sources
Helixi105 – 11511Combined sources
Helixi116 – 1205Combined sources
Beta strandi129 – 1357Combined sources
Beta strandi138 – 1436Combined sources
Helixi151 – 1588Combined sources
Helixi163 – 18422Combined sources
Helixi193 – 1953Combined sources
Beta strandi196 – 1983Combined sources
Turni200 – 2023Combined sources
Beta strandi204 – 2063Combined sources
Helixi213 – 2186Combined sources
Turni220 – 2223Combined sources
Helixi227 – 2293Combined sources
Helixi232 – 2354Combined sources
Helixi242 – 25817Combined sources
Helixi268 – 2758Combined sources
Helixi310 – 31910Combined sources
Turni327 – 3293Combined sources
Helixi332 – 34211Combined sources
Turni346 – 3483Combined sources
Helixi352 – 3565Combined sources
Helixi359 – 3668Combined sources
Helixi371 – 3799Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1S9JX-ray2.40A62-393[»]
2P55X-ray2.80A62-393[»]
3DV3X-ray2.30A62-382[»]
3DY7X-ray2.70A62-393[»]
3E8NX-ray2.50A62-393[»]
3EQBX-ray2.62A62-393[»]
3EQCX-ray1.80A35-393[»]
3EQDX-ray2.10A35-393[»]
3EQFX-ray2.70A35-393[»]
3EQGX-ray2.50A35-393[»]
3EQHX-ray2.00A35-393[»]
3EQIX-ray1.90A35-393[»]
3MBLX-ray2.60A62-382[»]
3ORNX-ray2.80A62-393[»]
3OS3X-ray2.80A62-393[»]
3PP1X-ray2.70A62-382[»]
3SLSX-ray2.30A/B45-263[»]
A/B308-383[»]
3V01X-ray2.70A62-393[»]
3V04X-ray2.70A62-393[»]
3VVHX-ray2.00A/B/C62-393[»]
3W8QX-ray2.20A39-382[»]
3WIGX-ray2.70A62-393[»]
3ZLSX-ray2.50A37-383[»]
3ZLWX-ray2.12A37-383[»]
3ZLXX-ray2.20A37-383[»]
3ZLYX-ray2.11A37-383[»]
3ZM4X-ray2.37A37-383[»]
4AN2X-ray2.50A61-392[»]
4AN3X-ray2.10A61-392[»]
4AN9X-ray2.80A61-392[»]
4ANBX-ray2.20A61-392[»]
4ARKX-ray2.60A62-393[»]
4LMNX-ray2.80A62-393[»]
4MNEX-ray2.85A/D/E/H62-393[»]
4U7ZX-ray2.80A62-393[»]
4U80X-ray2.80A62-393[»]
4U81X-ray2.70A62-393[»]
ProteinModelPortaliQ02750.
SMRiQ02750. Positions 29-382.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ02750.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini68 – 361294Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni77 – 782Inhibitor binding
Regioni144 – 1463Inhibitor binding
Regioni208 – 2125Inhibitor binding
Regioni270 – 30738RAF1-bindingBy similarityAdd
BLAST

Compositional bias

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

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ02750.
KOiK04368.
OMAiRDKHAIM.
OrthoDBiEOG7HF1KZ.
PhylomeDBiQ02750.
TreeFamiTF105137.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q02750-1) [UniParc]FASTAAdd to Basket

Also known as: MKK1a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL
60 70 80 90 100
EAFLTQKQKV GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH
110 120 130 140 150
LEIKPAIRNQ IIRELQVLHE CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS
160 170 180 190 200
LDQVLKKAGR IPEQILGKVS IAVIKGLTYL REKHKIMHRD VKPSNILVNS
210 220 230 240 250
RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY SVQSDIWSMG
260 270 280 290 300
LSLVEMAVGR YPIPPPDAKE LELMFGCQVE GDAAETPPRP RTPGRPLSSY
310 320 330 340 350
GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA
360 370 380 390
DLKQLMVHAF IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA AGV
Length:393
Mass (Da):43,439
Last modified:January 23, 2007 - v2
Checksum:i0344118FFC842D51
GO
Isoform 2 (identifier: Q02750-2) [UniParc]FASTAAdd to Basket

Also known as: MKK1b

The sequence of this isoform differs from the canonical sequence as follows:
     147-172: Missing.

Show »
Length:367
Mass (Da):40,764
Checksum:i9944432D8705DEFD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti53 – 531F → S in CFC3. 1 Publication
VAR_035093
Natural varianti128 – 1281G → V in CFC3. 1 Publication
VAR_069780
Natural varianti130 – 1301Y → C in CFC3. 1 Publication
VAR_035094

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei147 – 17226Missing in isoform 2. 1 PublicationVSP_040500Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L05624 mRNA. Translation: AAA36318.1.
L11284 mRNA. No translation available.
CCDSiCCDS10216.1. [Q02750-1]
PIRiA45100.
RefSeqiNP_002746.1. NM_002755.3. [Q02750-1]
XP_006720671.1. XM_006720608.1. [Q02750-2]
UniGeneiHs.145442.

Genome annotation databases

EnsembliENST00000307102; ENSP00000302486; ENSG00000169032. [Q02750-1]
GeneIDi5604.
KEGGihsa:5604.
UCSCiuc010bhq.3. human. [Q02750-1]

Polymorphism databases

DMDMi400274.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L05624 mRNA. Translation: AAA36318.1 .
L11284 mRNA. No translation available.
CCDSi CCDS10216.1. [Q02750-1 ]
PIRi A45100.
RefSeqi NP_002746.1. NM_002755.3. [Q02750-1 ]
XP_006720671.1. XM_006720608.1. [Q02750-2 ]
UniGenei Hs.145442.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1S9J X-ray 2.40 A 62-393 [» ]
2P55 X-ray 2.80 A 62-393 [» ]
3DV3 X-ray 2.30 A 62-382 [» ]
3DY7 X-ray 2.70 A 62-393 [» ]
3E8N X-ray 2.50 A 62-393 [» ]
3EQB X-ray 2.62 A 62-393 [» ]
3EQC X-ray 1.80 A 35-393 [» ]
3EQD X-ray 2.10 A 35-393 [» ]
3EQF X-ray 2.70 A 35-393 [» ]
3EQG X-ray 2.50 A 35-393 [» ]
3EQH X-ray 2.00 A 35-393 [» ]
3EQI X-ray 1.90 A 35-393 [» ]
3MBL X-ray 2.60 A 62-382 [» ]
3ORN X-ray 2.80 A 62-393 [» ]
3OS3 X-ray 2.80 A 62-393 [» ]
3PP1 X-ray 2.70 A 62-382 [» ]
3SLS X-ray 2.30 A/B 45-263 [» ]
A/B 308-383 [» ]
3V01 X-ray 2.70 A 62-393 [» ]
3V04 X-ray 2.70 A 62-393 [» ]
3VVH X-ray 2.00 A/B/C 62-393 [» ]
3W8Q X-ray 2.20 A 39-382 [» ]
3WIG X-ray 2.70 A 62-393 [» ]
3ZLS X-ray 2.50 A 37-383 [» ]
3ZLW X-ray 2.12 A 37-383 [» ]
3ZLX X-ray 2.20 A 37-383 [» ]
3ZLY X-ray 2.11 A 37-383 [» ]
3ZM4 X-ray 2.37 A 37-383 [» ]
4AN2 X-ray 2.50 A 61-392 [» ]
4AN3 X-ray 2.10 A 61-392 [» ]
4AN9 X-ray 2.80 A 61-392 [» ]
4ANB X-ray 2.20 A 61-392 [» ]
4ARK X-ray 2.60 A 62-393 [» ]
4LMN X-ray 2.80 A 62-393 [» ]
4MNE X-ray 2.85 A/D/E/H 62-393 [» ]
4U7Z X-ray 2.80 A 62-393 [» ]
4U80 X-ray 2.80 A 62-393 [» ]
4U81 X-ray 2.70 A 62-393 [» ]
ProteinModelPortali Q02750.
SMRi Q02750. Positions 29-382.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111590. 47 interactions.
DIPi DIP-201N.
IntActi Q02750. 27 interactions.
MINTi MINT-99632.
STRINGi 9606.ENSP00000302486.

Chemistry

BindingDBi Q02750.
ChEMBLi CHEMBL2111351.
DrugBanki DB06616. Bosutinib.
DB08911. Trametinib.
GuidetoPHARMACOLOGYi 2062.

PTM databases

PhosphoSitei Q02750.

Polymorphism databases

DMDMi 400274.

Proteomic databases

MaxQBi Q02750.
PaxDbi Q02750.
PeptideAtlasi Q02750.
PRIDEi Q02750.

Protocols and materials databases

DNASUi 5604.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000307102 ; ENSP00000302486 ; ENSG00000169032 . [Q02750-1 ]
GeneIDi 5604.
KEGGi hsa:5604.
UCSCi uc010bhq.3. human. [Q02750-1 ]

Organism-specific databases

CTDi 5604.
GeneCardsi GC15P066679.
GeneReviewsi MAP2K1.
HGNCi HGNC:6840. MAP2K1.
HPAi CAB003834.
HPA026430.
MIMi 176872. gene.
615279. phenotype.
neXtProti NX_Q02750.
Orphaneti 1340. Cardiofaciocutaneous syndrome.
PharmGKBi PA30584.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000119199.
HOGENOMi HOG000234206.
HOVERGENi HBG108518.
InParanoidi Q02750.
KOi K04368.
OMAi RDKHAIM.
OrthoDBi EOG7HF1KZ.
PhylomeDBi Q02750.
TreeFami TF105137.

Enzyme and pathway databases

BRENDAi 2.7.12.2. 2681.
Reactomei REACT_1391. ERK1 activation.
REACT_22272. Signal transduction by L1.
REACT_22442. Interleukin-1 signaling.
REACT_228255. Uptake and function of anthrax toxins.
REACT_614. RAF phosphorylates MEK.
REACT_9470. Signaling by FGFR.
REACT_962. MEK activation.
SignaLinki Q02750.

Miscellaneous databases

ChiTaRSi MAP2K1. human.
EvolutionaryTracei Q02750.
GeneWikii MAP2K1.
GenomeRNAii 5604.
NextBioi 21776.
PMAP-CutDB Q02750.
PROi Q02750.
SOURCEi Search...

Gene expression databases

Bgeei Q02750.
CleanExi HS_MAP2K1.
ExpressionAtlasi Q02750. baseline and differential.
Genevestigatori Q02750.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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. "Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases."
    Seger R., Seger D., Lozeman F.J., Ahn N.G., Graves L.M., Campbell J.S., Ericsson L., Harrylock M., Jensen A.M., Krebs E.G.
    J. Biol. Chem. 267:25628-25631(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PARTIAL PROTEIN SEQUENCE, TISSUE SPECIFICITY.
    Tissue: T-cell.
  2. "Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2."
    Zheng C.-F., Guan K.-L.
    J. Biol. Chem. 268:11435-11439(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues."
    Zheng C.-F., Guan K.-L.
    EMBO J. 13:1123-1131(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-218 AND SER-222, MUTAGENESIS.
  4. Cited for: CLEAVAGE BY ANTHRAX LETHAL FACTOR, PROTEIN SEQUENCE OF 9-17.
  5. "Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor."
    Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.
    Biochem. J. 352:739-745(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY ANTHRAX LETHAL FACTOR.
  6. "The MAP kinase pathway is required for entry into mitosis and cell survival."
    Liu X., Yan S., Zhou T., Terada Y., Erikson R.L.
    Oncogene 23:763-776(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, FUNCTION.
  7. "Role of group A p21-activated kinases in activation of extracellular-regulated kinase by growth factors."
    Beeser A., Jaffer Z.M., Hofmann C., Chernoff J.
    J. Biol. Chem. 280:36609-36615(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-298.
  8. "Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation."
    Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J., Orth K.
    Science 312:1211-1214(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH YOPJ, ACETYLATION.
  9. "Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma."
    Burgermeister E., Chuderland D., Hanoch T., Meyer M., Liscovitch M., Seger R.
    Mol. Cell. Biol. 27:803-817(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PPARG.
  10. "Final stages of cytokinesis and midbody ring formation are controlled by BRUCE."
    Pohl C., Jentsch S.
    Cell 132:832-845(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BIRC6/BRUCE.
  11. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-286, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  12. "Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration."
    Won M., Park K.A., Byun H.S., Kim Y.R., Choi B.L., Hong J.H., Park J., Seok J.H., Lee Y.H., Cho C.H., Song I.S., Kim Y.K., Shen H.M., Hur G.M.
    J. Hepatol. 51:67-76(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SGK1.
  13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  14. "VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer."
    Fernandez I.F., Blanco S., Lozano J., Lazo P.A.
    Mol. Cell. Biol. 30:4687-4697(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VRK2.
  15. Cited for: REVIEW ON FUNCTION.
  16. Cited for: REVIEW ON ENZYME REGULATION.
  17. "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.
  18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  19. "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.
  20. Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 62-392 IN COMPLEX WITH ATP AND INHIBITOR.
  21. Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP AND INHIBITOR.
  22. "2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase)."
    Warmus J.S., Flamme C., Zhang L.Y., Barrett S., Bridges A., Chen H., Gowan R., Kaufman M., Sebolt-Leopold J., Leopold W., Merriman R., Ohren J., Pavlovsky A., Przybranowski S., Tecle H., Valik H., Whitehead C., Zhang E.
    Bioorg. Med. Chem. Lett. 18:6171-6174(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP AND INHIBITOR.
  23. "Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors."
    Fischmann T.O., Smith C.K., Mayhood T.W., Myers J.E., Reichert P., Mannarino A., Carr D., Zhu H., Wong J., Yang R.S., Le H.V., Madison V.S.
    Biochemistry 48:2661-2674(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 35-393 IN COMPLEX WITH ADP AND INHIBITOR.
  24. "Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?"
    Tecle H., Shao J., Li Y., Kothe M., Kazmirski S., Penzotti J., Ding Y.H., Ohren J., Moshinsky D., Coli R., Jhawar N., Bora E., Jacques-O'Hagan S., Wu J.
    Bioorg. Med. Chem. Lett. 19:226-229(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 62-382 IN COMPLEX WITH ATP AND INHIBITOR.
  25. "RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer."
    Iverson C., Larson G., Lai C., Yeh L.T., Dadson C., Weingarten P., Appleby T., Vo T., Maderna A., Vernier J.M., Hamatake R., Miner J.N., Quart B.
    Cancer Res. 69:6839-6847(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP AND INHIBITOR.
  26. Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 62-382 IN COMPLEX WITH ADP AND INHIBITOR.
  27. "Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer."
    Dong Q., Dougan D.R., Gong X., Halkowycz P., Jin B., Kanouni T., O'Connell S.M., Scorah N., Shi L., Wallace M.B., Zhou F.
    Bioorg. Med. Chem. Lett. 21:1315-1319(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 62-382 IN COMPLEX WITH ATP AND INHIBITOR.
  28. Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 62-393.
  29. "Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome."
    Rodriguez-Viciana P., Tetsu O., Tidyman W.E., Estep A.L., Conger B.A., Cruz M.S., McCormick F., Rauen K.A.
    Science 311:1287-1290(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CFC3 SER-53 AND CYS-130.
  30. Cited for: VARIANT CFC3 VAL-128.

Entry informationi

Entry nameiMP2K1_HUMAN
AccessioniPrimary (citable) accession number: Q02750
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: November 26, 2014
This is version 165 of the entry and version 2 of the sequence. [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 15
    Human chromosome 15: 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

External Data

Dasty 3