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Protein

Dual specificity mitogen-activated protein kinase kinase 6

Gene

MAP2K6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 – 821ATPPROSITE-ProRule annotation
Active sitei179 – 1791Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi59 – 679ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase kinase activity Source: ProtInc
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: GO_Central
  • protein tyrosine kinase activity Source: UniProtKB-KW

GO - Biological processi

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_264618. Uptake and function of anthrax toxins.
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 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:6846. MAP2K6.

Subcellular locationi

GO - Cellular componenti

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.

Polymorphism and mutation databases

BioMutaiMAP2K6.
DMDMi1709088.

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei207 – 2071O-acetylserine; by Yersinia yopJ; alternate1 Publication
Modified residuei207 – 2071Phosphoserine; by MAP3K; alternate1 Publication
Modified residuei211 – 2111O-acetylthreonine; by Yersinia yopJ; alternate1 Publication
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/TAOK2.1 Publication
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.

Gene expression databases

BgeeiP52564.
CleanExiHS_MAP2K6.
ExpressionAtlasiP52564. baseline and differential.
GenevisibleiP52564. HS.

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.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GADD45AP245222EBI-448135,EBI-448167
LRRK2Q5S0074EBI-448135,EBI-5323863
MAP3K4Q9Y6R42EBI-448135,EBI-448104

Protein-protein interaction databases

BioGridi111594. 21 interactions.
DIPiDIP-31346N.
IntActiP52564. 11 interactions.
MINTiMINT-3019559.
STRINGi9606.ENSP00000468348.

Structurei

Secondary structure

1
334
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi50 – 523Combined sources
Beta strandi53 – 619Combined sources
Beta strandi63 – 7210Combined sources
Turni73 – 764Combined sources
Beta strandi77 – 848Combined sources
Helixi90 – 10415Combined sources
Turni110 – 1123Combined sources
Beta strandi115 – 1206Combined sources
Beta strandi122 – 1309Combined sources
Beta strandi133 – 1353Combined sources
Helixi136 – 14510Combined sources
Helixi152 – 17221Combined sources
Helixi182 – 1843Combined sources
Beta strandi185 – 1873Combined sources
Beta strandi193 – 1953Combined sources
Helixi201 – 2033Combined sources
Helixi207 – 2126Combined sources
Helixi222 – 2254Combined sources
Helixi236 – 25217Combined sources
Helixi263 – 27210Combined sources
Turni280 – 2823Combined sources
Helixi285 – 29410Combined sources
Helixi299 – 3013Combined sources
Helixi305 – 3084Combined sources
Helixi312 – 3198Combined sources
Helixi324 – 3329Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52564.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini53 – 314262Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni4 – 1916D domainBy similarityAdd
BLAST
Regioni311 – 33424DVD domainAdd
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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiP52564.
KOiK04433.
OMAiKEYTARP.
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.
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. AlignAdd to basket

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

        10         20         30         40         50
MSQSKGKKRN PGLKIPKEAF EQPQTSSTPP RDLDSKACIS IGNQNFEVKA
60 70 80 90 100
DDLEPIMELG RGAYGVVEKM RHVPSGQIMA VKRIRATVNS QEQKRLLMDL
110 120 130 140 150
DISMRTVDCP FTVTFYGALF REGDVWICME LMDTSLDKFY KQVIDKGQTI
160 170 180 190 200
PEDILGKIAV SIVKALEHLH SKLSVIHRDV KPSNVLINAL GQVKMCDFGI
210 220 230 240 250
SGYLVDSVAK TIDAGCKPYM APERINPELN QKGYSVKSDI WSLGITMIEL
260 270 280 290 300
AILRFPYDSW GTPFQQLKQV VEEPSPQLPA DKFSAEFVDF TSQCLKKNSK
310 320 330
ERPTYPELMQ HPFFTLHESK GTDVASFVKL ILGD
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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti125 – 1251V → M in AAB03705 (PubMed:8621675).Curated
Sequence conflicti125 – 1251V → M in AAB03708 (PubMed:8621675).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5656Missing in isoform 2. 1 PublicationVSP_004882Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

EnsembliENST00000590474; ENSP00000468348; ENSG00000108984.
GeneIDi5608.
KEGGihsa:5608.
UCSCiuc002jii.3. human. [P52564-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111594. 21 interactions.
DIPiDIP-31346N.
IntActiP52564. 11 interactions.
MINTiMINT-3019559.
STRINGi9606.ENSP00000468348.

Chemistry

BindingDBiP52564.
ChEMBLiCHEMBL2171.
GuidetoPHARMACOLOGYi2067.

PTM databases

PhosphoSiteiP52564.

Polymorphism and mutation databases

BioMutaiMAP2K6.
DMDMi1709088.

Proteomic databases

MaxQBiP52564.
PaxDbiP52564.
PRIDEiP52564.

Protocols and materials databases

DNASUi5608.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000590474; ENSP00000468348; ENSG00000108984.
GeneIDi5608.
KEGGihsa:5608.
UCSCiuc002jii.3. human. [P52564-1]

Organism-specific databases

CTDi5608.
GeneCardsiGC17P067410.
HGNCiHGNC:6846. MAP2K6.
HPAiCAB007744.
HPA031134.
MIMi601254. gene.
neXtProtiNX_P52564.
PharmGKBiPA30591.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiP52564.
KOiK04433.
OMAiKEYTARP.
OrthoDBiEOG7J9VPW.
PhylomeDBiP52564.

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_264618. Uptake and function of anthrax toxins.
REACT_75776. NOD1/2 Signaling Pathway.
SignaLinkiP52564.

Miscellaneous databases

ChiTaRSiMAP2K6. human.
EvolutionaryTraceiP52564.
GeneWikiiMAP2K6.
GenomeRNAii5608.
NextBioi21798.
PMAP-CutDBP52564.
PROiP52564.
SOURCEiSearch...

Gene expression databases

BgeeiP52564.
CleanExiHS_MAP2K6.
ExpressionAtlasiP52564. baseline and differential.
GenevisibleiP52564. HS.

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]
ProtoNetiSearch...

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: July 22, 2015
This is version 160 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.