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P52564

- MP2K6_HUMAN

UniProt

P52564 - MP2K6_HUMAN

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Protein
Dual specificity mitogen-activated protein kinase kinase 6
Gene
MAP2K6, MEK6, MKK6, PRKMK6, SKK3
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. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by dual phosphorylation on Ser-207 and Thr-211 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei14 – 152Cleavage; by anthrax lethal factor
Binding sitei82 – 821ATP By similarity
Active sitei179 – 1791Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi59 – 679ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase kinase activity Source: RefGenome
  3. protein binding Source: UniProtKB
  4. protein kinase binding Source: UniProtKB
  5. protein tyrosine kinase activity Source: UniProtKB-KW
  6. receptor signaling protein serine/threonine kinase activity Source: RefGenome

GO - Biological processi

  1. DNA damage induced protein phosphorylation Source: ProtInc
  2. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  3. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  4. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  5. activation of MAPK activity Source: Reactome
  6. apoptotic process Source: UniProtKB-KW
  7. cardiac muscle contraction Source: Ensembl
  8. cell cycle arrest Source: ProtInc
  9. cellular response to sorbitol Source: Ensembl
  10. innate immune response Source: Reactome
  11. muscle cell differentiation Source: Reactome
  12. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
  13. nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  14. positive regulation of apoptotic process Source: Ensembl
  15. positive regulation of muscle cell differentiation Source: Reactome
  16. regulation of transcription, DNA-templated Source: UniProtKB-KW
  17. response to drug Source: Ensembl
  18. response to ischemia Source: Ensembl
  19. signal transduction Source: ProtInc
  20. stress-activated MAPK cascade Source: Reactome
  21. toll-like receptor 10 signaling pathway Source: Reactome
  22. toll-like receptor 2 signaling pathway Source: Reactome
  23. toll-like receptor 3 signaling pathway Source: Reactome
  24. toll-like receptor 4 signaling pathway Source: Reactome
  25. toll-like receptor 5 signaling pathway Source: Reactome
  26. toll-like receptor 9 signaling pathway Source: Reactome
  27. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  28. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  29. toll-like receptor signaling pathway Source: Reactome
  30. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Apoptosis, Stress response, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 2681.
ReactomeiREACT_169436. Oxidative Stress Induced Senescence.
REACT_21399. activated TAK1 mediates p38 MAPK activation.
REACT_21402. CDO in myogenesis.
REACT_22442. Interleukin-1 signaling.
REACT_75776. NOD1/2 Signaling Pathway.
SignaLinkiP52564.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 6 (EC:2.7.12.2)
Short name:
MAP kinase kinase 6
Short name:
MAPKK 6
Alternative name(s):
MAPK/ERK kinase 6
Short name:
MEK 6
Stress-activated protein kinase kinase 3
Short name:
SAPK kinase 3
Short name:
SAPKK-3
Short name:
SAPKK3
Gene namesi
Name:MAP2K6
Synonyms:MEK6, MKK6, PRKMK6, SKK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:6846. MAP2K6.

Subcellular locationi

Nucleus. Cytoplasm. Cytoplasmcytoskeleton
Note: Binds to microtubules.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: RefGenome
  2. cytoskeleton Source: UniProtKB-SubCell
  3. cytosol Source: Reactome
  4. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi207 – 2071S → A: Inactivation.
Mutagenesisi207 – 2071S → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.
Mutagenesisi211 – 2111T → A: Inactivation.
Mutagenesisi211 – 2111T → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.

Organism-specific databases

PharmGKBiPA30591.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 334334Dual specificity mitogen-activated protein kinase kinase 6
PRO_0000086386Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei207 – 2071O-acetylserine; by Yersinia yopJ; alternate
Modified residuei207 – 2071Phosphoserine; by MAP3K; alternate1 Publication
Modified residuei211 – 2111O-acetylthreonine; by Yersinia yopJ; alternate
Modified residuei211 – 2111Phosphothreonine; by MAP3K; alternate1 Publication

Post-translational modificationi

Weakly autophosphorylated. Phosphorylated at Ser-207 and Thr-211 by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.11 Publications
Acetylation of Ser-207 and Thr-211 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP52564.
PaxDbiP52564.
PRIDEiP52564.

PTM databases

PhosphoSiteiP52564.

Miscellaneous databases

PMAP-CutDBP52564.

Expressioni

Tissue specificityi

Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas.1 Publication

Inductioni

Strongly activated by UV, anisomycin, and osmotic shock but not by phorbol esters, NGF or EGF.3 Publications

Gene expression databases

ArrayExpressiP52564.
BgeeiP52564.
CleanExiHS_MAP2K6.
GenevestigatoriP52564.

Organism-specific databases

HPAiCAB007744.
HPA031134.

Interactioni

Subunit structurei

Dimer. Interacts with Yersinia yopJ. Interacts (via its D domain) with its substrates MAPK11, MAPK12, MAPK13 and MAPK14 By similarity. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2 By similarity. Interacts with DCTN1. Interacts with EIF2AK2/PKR.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LRRK2Q5S0074EBI-448135,EBI-5323863

Protein-protein interaction databases

BioGridi111594. 19 interactions.
DIPiDIP-31346N.
IntActiP52564. 8 interactions.
MINTiMINT-3019559.
STRINGi9606.ENSP00000351997.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi50 – 523
Beta strandi53 – 619
Beta strandi63 – 7210
Turni73 – 764
Beta strandi77 – 848
Helixi90 – 10415
Turni110 – 1123
Beta strandi115 – 1206
Beta strandi122 – 1309
Beta strandi133 – 1353
Helixi136 – 14510
Helixi152 – 17221
Helixi182 – 1843
Beta strandi185 – 1873
Beta strandi193 – 1953
Helixi201 – 2033
Helixi207 – 2126
Helixi222 – 2254
Helixi236 – 25217
Helixi263 – 27210
Turni280 – 2823
Helixi285 – 29410
Helixi299 – 3013
Helixi305 – 3084
Helixi312 – 3198
Helixi324 – 3329

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Y8OX-ray1.95B4-17[»]
3ENMX-ray2.35A/B/C/D45-332[»]
3FMEX-ray2.26A47-334[»]
3VN9X-ray2.60A1-334[»]
ProteinModelPortaliP52564.
SMRiP52564. Positions 44-334.

Miscellaneous databases

EvolutionaryTraceiP52564.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini53 – 314262Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni4 – 1916D domain By similarity
Add
BLAST
Regioni311 – 33424DVD domain
Add
BLAST

Domaini

The DVD domain (residues 311-334) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.1 Publication
The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates By similarity.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiP52564.
KOiK04433.
OMAiESAVAMV.
OrthoDBiEOG7J9VPW.
PhylomeDBiP52564.

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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P52564-1) [UniParc]FASTAAdd to Basket

Also known as: MKK6b

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

MSQSKGKKRN PGLKIPKEAF EQPQTSSTPP RDLDSKACIS IGNQNFEVKA    50
DDLEPIMELG RGAYGVVEKM RHVPSGQIMA VKRIRATVNS QEQKRLLMDL 100
DISMRTVDCP FTVTFYGALF REGDVWICME LMDTSLDKFY KQVIDKGQTI 150
PEDILGKIAV SIVKALEHLH SKLSVIHRDV KPSNVLINAL GQVKMCDFGI 200
SGYLVDSVAK TIDAGCKPYM APERINPELN QKGYSVKSDI WSLGITMIEL 250
AILRFPYDSW GTPFQQLKQV VEEPSPQLPA DKFSAEFVDF TSQCLKKNSK 300
ERPTYPELMQ HPFFTLHESK GTDVASFVKL ILGD 334
Length:334
Mass (Da):37,492
Last modified:October 1, 1996 - v1
Checksum:i4ECA8014522216AF
GO
Isoform 2 (identifier: P52564-2) [UniParc]FASTAAdd to Basket

Also known as: MKK6

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.

Show »
Length:278
Mass (Da):31,339
Checksum:i1EE7FC1B26B11AE4
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5656Missing in isoform 2.
VSP_004882Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti125 – 1251V → M in AAB03705. 1 Publication
Sequence conflicti125 – 1251V → M in AAB03708. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U39657 mRNA. Translation: AAC50389.1.
U39656 mRNA. Translation: AAC50388.1.
U49732 mRNA. Translation: AAB05035.1.
U39065 mRNA. Translation: AAB03705.1.
U39064 mRNA. Translation: AAB03708.1.
D87905 mRNA. Translation: BAA13496.1.
X96757 mRNA. Translation: CAA65532.1.
BC012009 mRNA. Translation: AAH12009.1.
CCDSiCCDS11686.1. [P52564-1]
PIRiS71631.
RefSeqiNP_002749.2. NM_002758.3. [P52564-1]
UniGeneiHs.463978.

Genome annotation databases

EnsembliENST00000589647; ENSP00000467213; ENSG00000108984. [P52564-2]
ENST00000590474; ENSP00000468348; ENSG00000108984. [P52564-1]
GeneIDi5608.
KEGGihsa:5608.
UCSCiuc002jii.3. human. [P52564-1]

Polymorphism databases

DMDMi1709088.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U39657 mRNA. Translation: AAC50389.1 .
U39656 mRNA. Translation: AAC50388.1 .
U49732 mRNA. Translation: AAB05035.1 .
U39065 mRNA. Translation: AAB03705.1 .
U39064 mRNA. Translation: AAB03708.1 .
D87905 mRNA. Translation: BAA13496.1 .
X96757 mRNA. Translation: CAA65532.1 .
BC012009 mRNA. Translation: AAH12009.1 .
CCDSi CCDS11686.1. [P52564-1 ]
PIRi S71631.
RefSeqi NP_002749.2. NM_002758.3. [P52564-1 ]
UniGenei Hs.463978.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2Y8O X-ray 1.95 B 4-17 [» ]
3ENM X-ray 2.35 A/B/C/D 45-332 [» ]
3FME X-ray 2.26 A 47-334 [» ]
3VN9 X-ray 2.60 A 1-334 [» ]
ProteinModelPortali P52564.
SMRi P52564. Positions 44-334.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111594. 19 interactions.
DIPi DIP-31346N.
IntActi P52564. 8 interactions.
MINTi MINT-3019559.
STRINGi 9606.ENSP00000351997.

Chemistry

BindingDBi P52564.
ChEMBLi CHEMBL2171.
GuidetoPHARMACOLOGYi 2067.

PTM databases

PhosphoSitei P52564.

Polymorphism databases

DMDMi 1709088.

Proteomic databases

MaxQBi P52564.
PaxDbi P52564.
PRIDEi P52564.

Protocols and materials databases

DNASUi 5608.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000589647 ; ENSP00000467213 ; ENSG00000108984 . [P52564-2 ]
ENST00000590474 ; ENSP00000468348 ; ENSG00000108984 . [P52564-1 ]
GeneIDi 5608.
KEGGi hsa:5608.
UCSCi uc002jii.3. human. [P52564-1 ]

Organism-specific databases

CTDi 5608.
GeneCardsi GC17P067410.
HGNCi HGNC:6846. MAP2K6.
HPAi CAB007744.
HPA031134.
MIMi 601254. gene.
neXtProti NX_P52564.
PharmGKBi PA30591.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000234206.
HOVERGENi HBG108518.
InParanoidi P52564.
KOi K04433.
OMAi ESAVAMV.
OrthoDBi EOG7J9VPW.
PhylomeDBi P52564.

Enzyme and pathway databases

BRENDAi 2.7.12.2. 2681.
Reactomei REACT_169436. Oxidative Stress Induced Senescence.
REACT_21399. activated TAK1 mediates p38 MAPK activation.
REACT_21402. CDO in myogenesis.
REACT_22442. Interleukin-1 signaling.
REACT_75776. NOD1/2 Signaling Pathway.
SignaLinki P52564.

Miscellaneous databases

EvolutionaryTracei P52564.
GeneWikii MAP2K6.
GenomeRNAii 5608.
NextBioi 21798.
PMAP-CutDB P52564.
PROi P52564.
SOURCEi Search...

Gene expression databases

ArrayExpressi P52564.
Bgeei P52564.
CleanExi HS_MAP2K6.
Genevestigatori P52564.

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. "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway."
    Raingeaud J., Whitmarsh A.J., Barrett T., Derijard B., Davis R.J.
    Mol. Cell. Biol. 16:1247-1255(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS, FUNCTION.
    Tissue: Skeletal muscle.
  2. "Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade."
    Stein B., Brady H., Yang M.X., Young D.B., Barbosa M.S.
    J. Biol. Chem. 271:11427-11433(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION.
    Tissue: T-cell.
  3. "Characterization of the structure and function of a novel MAP kinase kinase (MKK6)."
    Han J., Lee J.-D., Jiang Y., Li Z., Feng L., Ulevitch R.J.
    J. Biol. Chem. 271:2886-2891(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, MUTAGENESIS.
    Tissue: Placenta.
  4. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION, ENZYME REGULATION, FUNCTION.
  5. "Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells."
    Cuenda A., Alonso G., Morrice N., Jones M., Meier R., Cohen P., Nebreda A.R.
    EMBO J. 15:4156-4164(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  6. "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] (ISOFORM 1).
    Tissue: Urinary bladder.
  7. "Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases."
    Goedert M., Cuenda A., Craxton M., Jakes R., Cohen P.
    EMBO J. 16:3563-3571(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ACTIVATION OF MAPK13.
  8. "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2."
    Ben-Levy R., Hooper S., Wilson R., Paterson H.F., Marshall C.J.
    Curr. Biol. 8:1049-1057(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  9. "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades."
    Chan-Hui P.Y., Weaver R.
    Biochem. J. 336:599-609(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY MAP3K4.
  10. "MEK kinase 3 directly activates MKK6 and MKK7, specific activators of the p38 and c-Jun NH2-terminal kinases."
    Deacon K., Blank J.L.
    J. Biol. Chem. 274:16604-16610(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY MAP3K2/MEKK2 AND MAP3K3/MEK3.
  11. "Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain."
    Chen Z., Hutchison M., Cobb M.H.
    J. Biol. Chem. 274:28803-28807(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TAOK2, PHOSPHORYLATION BY TAOK2.
  12. "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway."
    Ninomiya-Tsuji J., Kishimoto K., Hiyama A., Inoue J., Cao Z., Matsumoto K.
    Nature 398:252-256(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY MAP3K7/TAK1.
  13. "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.
  14. "Importance of the MKK6/p38 pathway for interleukin-12-induced STAT4 serine phosphorylation and transcriptional activity."
    Visconti R., Gadina M., Chiariello M., Chen E.H., Stancato L.F., Gutkind J.S., O'Shea J.J.
    Blood 96:1844-1852(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  15. "The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription."
    Bode J.G., Ludwig S., Freitas C.A., Schaper F., Ruhl M., Melmed S., Heinrich P.C., Haussinger D.
    Biol. Chem. 382:1447-1453(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  16. "Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress."
    Morita K., Saitoh M., Tobiume K., Matsuura H., Enomoto S., Nishitoh H., Ichijo H.
    EMBO J. 20:6028-6036(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY MAP3K5/ASK1.
  17. "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2."
    Chen Z., Cobb M.H.
    J. Biol. Chem. 276:16070-16075(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY TAOK2.
  18. "TAK1 is a ubiquitin-dependent kinase of MKK and IKK."
    Wang C., Deng L., Hong M., Akkaraju G.R., Inoue J., Chen Z.J.
    Nature 412:346-351(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY MAP3K7/TAK1.
  19. "Protein kinase R (PKR) interacts with and activates mitogen-activated protein kinase kinase 6 (MKK6) in response to double-stranded RNA stimulation."
    Silva A.M., Whitmore M., Xu Z., Jiang Z., Li X., Williams B.R.
    J. Biol. Chem. 279:37670-37676(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EIF2AK2, PHOSPHORYLATION.
  20. "p150(Glued), Dynein, and microtubules are specifically required for activation of MKK3/6 and p38 MAPKs."
    Cheung P.Y., Zhang Y., Long J., Lin S., Zhang M., Jiang Y., Wu Z.
    J. Biol. Chem. 279:45308-45311(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DCTN1, MICROTUBULE-BINDING.
  21. "Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP kinase."
    Kaur R., Liu X., Gjoerup O., Zhang A., Yuan X., Balk S.P., Schneider M.C., Lu M.L.
    J. Biol. Chem. 280:3323-3330(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PAK6.
  22. "Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases."
    Takekawa M., Tatebayashi K., Saito H.
    Mol. Cell 18:295-306(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN.
  23. "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: ACETYLATION AT SER-207 AND THR-211, PHOSPHORYLATION AT SER-207 AND THR-211, INACTIVATION BY YERSINIA YOPJ, IDENTIFICATION BY MASS SPECTROMETRY.
  24. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  25. "Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation."
    Sturchler E., Feurstein D., McDonald P., Duckett D.
    Biochemistry 49:4094-4102(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY MAP3K5/ASK1, ENZYME REGULATION, IDENTIFICATION BY MASS SPECTROMETRY.
  26. "MKK6 increases the melanocyte dendricity through the regulation of Rho family GTPases."
    Kim M.Y., Choi T.Y., Kim J.H., Lee J.H., Kim J.G., Sohn K.C., Yoon K.S., Kim C.D., Lee J.H., Yoon T.J.
    J. Dermatol. Sci. 60:114-119(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  27. Cited for: REVIEW ON ENZYME REGULATION, REVIEW ON FUNCTION.
  28. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  29. Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 45-332 OF MUTANT ASP-207 AND ASP-211, SUBUNIT.
  30. "Crystal structure of human mitogen-activated protein kinase kinase 6 (mek6) activated mutant (s207d, t211d)."
    Structural genomics consortium (SGC)
    Submitted (JUL-2011) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 47-334.

Entry informationi

Entry nameiMP2K6_HUMAN
AccessioniPrimary (citable) accession number: P52564
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 3, 2014
This is version 149 of the entry and version 1 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, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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