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P52564 (MP2K6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity mitogen-activated protein kinase kinase 6

Short name=MAP kinase kinase 6
Short name=MAPKK 6
EC=2.7.12.2
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 names
Name:MAP2K6
Synonyms:MEK6, MKK6, PRKMK6, SKK3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length334 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.4 Ref.7 Ref.14 Ref.15 Ref.21 Ref.26

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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. Ref.2 Ref.4 Ref.25

Subunit structure

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. Ref.11 Ref.19 Ref.20 Ref.29

Subcellular location

Nucleus. Cytoplasm. Cytoplasmcytoskeleton. Note: Binds to microtubules. Ref.8

Tissue specificity

Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas. Ref.3

Induction

Strongly activated by UV, anisomycin, and osmotic shock but not by phorbol esters, NGF or EGF. Ref.2 Ref.4 Ref.25

Domain

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. Ref.22

The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates By similarity. Ref.22

Post-translational modification

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. Ref.4 Ref.9 Ref.10 Ref.11 Ref.12 Ref.16 Ref.17 Ref.18 Ref.19 Ref.23 Ref.25

Acetylation of Ser-207 and Thr-211 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. Ref.23

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Stress response
Transcription
Transcription regulation
   Cellular componentCytoplasm
Cytoskeleton
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage induced protein phosphorylation

Traceable author statement PubMed 10848581. Source: ProtInc

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Traceable author statement. Source: Reactome

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cardiac muscle contraction

Inferred from electronic annotation. Source: Ensembl

cell cycle arrest

Traceable author statement PubMed 10848581. Source: ProtInc

cellular response to sorbitol

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

muscle cell differentiation

Traceable author statement. Source: Reactome

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of muscle cell differentiation

Traceable author statement. Source: Reactome

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ischemia

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.3. Source: ProtInc

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MAP kinase kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction Ref.19. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.17. Source: UniProtKB

protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

receptor signaling protein serine/threonine kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LRRK2Q5S0074EBI-448135,EBI-5323863

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P52564-1)

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.
Isoform 2 (identifier: P52564-2)

Also known as: MKK6;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 334334Dual specificity mitogen-activated protein kinase kinase 6
PRO_0000086386

Regions

Domain53 – 314262Protein kinase
Nucleotide binding59 – 679ATP By similarity
Region4 – 1916D domain By similarity
Region311 – 33424DVD domain

Sites

Active site1791Proton acceptor By similarity
Binding site821ATP By similarity
Site14 – 152Cleavage; by anthrax lethal factor

Amino acid modifications

Modified residue2071O-acetylserine; by Yersinia yopJ; alternate
Modified residue2071Phosphoserine; by MAP3K; alternate Ref.23
Modified residue2111O-acetylthreonine; by Yersinia yopJ; alternate
Modified residue2111Phosphothreonine; by MAP3K; alternate Ref.23

Natural variations

Alternative sequence1 – 5656Missing in isoform 2.
VSP_004882

Experimental info

Mutagenesis2071S → A: Inactivation.
Mutagenesis2071S → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.
Mutagenesis2111T → A: Inactivation.
Mutagenesis2111T → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.
Sequence conflict1251V → M in AAB03705. Ref.3
Sequence conflict1251V → M in AAB03708. Ref.3

Secondary structure

................................................ 334
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (MKK6b) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 4ECA8014522216AF

FASTA33437,492
        10         20         30         40         50         60 
MSQSKGKKRN PGLKIPKEAF EQPQTSSTPP RDLDSKACIS IGNQNFEVKA DDLEPIMELG 

        70         80         90        100        110        120 
RGAYGVVEKM RHVPSGQIMA VKRIRATVNS QEQKRLLMDL DISMRTVDCP FTVTFYGALF 

       130        140        150        160        170        180 
REGDVWICME LMDTSLDKFY KQVIDKGQTI PEDILGKIAV SIVKALEHLH SKLSVIHRDV 

       190        200        210        220        230        240 
KPSNVLINAL GQVKMCDFGI SGYLVDSVAK TIDAGCKPYM APERINPELN QKGYSVKSDI 

       250        260        270        280        290        300 
WSLGITMIEL AILRFPYDSW GTPFQQLKQV VEEPSPQLPA DKFSAEFVDF TSQCLKKNSK 

       310        320        330 
ERPTYPELMQ HPFFTLHESK GTDVASFVKL ILGD 

« Hide

Isoform 2 (MKK6) [UniParc].

Checksum: 1EE7FC1B26B11AE4
Show »

FASTA27831,339

References

« Hide 'large scale' references
[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]"A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3."
Moriguchi T., Kuroyanagi N., Yamaguchi K., Gotoh Y., Irie K., Kano T., Shirakabe K., Muro Y., Shibuya H., Matsumoto K., Nishida E., Hagiwara M.
J. Biol. Chem. 271:13675-13679(1996) [PubMed] [Europe PMC] [Abstract]
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Signaling by dual specificity kinases."
Dhanasekaran N., Premkumar Reddy E.
Oncogene 17:1447-1455(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ENZYME REGULATION, REVIEW ON FUNCTION.
[28]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]"The structure of the MAP2K MEK6 reveals an autoinhibitory dimer."
Min X., Akella R., He H., Humphreys J.M., Tsutakawa S.E., Lee S.J., Tainer J.A., Cobb M.H., Goldsmith E.J.
Structure 17:96-104(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS11686.1. [P52564-1]
PIRS71631.
RefSeqNP_002749.2. NM_002758.3. [P52564-1]
XP_005257572.1. XM_005257515.1. [P52564-2]
XP_005257573.1. XM_005257516.1. [P52564-2]
XP_005257574.1. XM_005257517.1. [P52564-2]
XP_006722038.1. XM_006721975.1. [P52564-2]
UniGeneHs.463978.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2Y8OX-ray1.95B4-17[»]
3ENMX-ray2.35A/B/C/D45-332[»]
3FMEX-ray2.26A47-334[»]
3VN9X-ray2.60A1-334[»]
ProteinModelPortalP52564.
SMRP52564. Positions 44-334.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111594. 19 interactions.
DIPDIP-31346N.
IntActP52564. 8 interactions.
MINTMINT-3019559.
STRING9606.ENSP00000351997.

Chemistry

BindingDBP52564.
ChEMBLCHEMBL2171.
GuidetoPHARMACOLOGY2067.

PTM databases

PhosphoSiteP52564.

Polymorphism databases

DMDM1709088.

Proteomic databases

MaxQBP52564.
PaxDbP52564.
PRIDEP52564.

Protocols and materials databases

DNASU5608.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000589647; ENSP00000467213; ENSG00000108984. [P52564-2]
ENST00000590474; ENSP00000468348; ENSG00000108984. [P52564-1]
GeneID5608.
KEGGhsa:5608.
UCSCuc002jii.3. human. [P52564-1]

Organism-specific databases

CTD5608.
GeneCardsGC17P067410.
HGNCHGNC:6846. MAP2K6.
HPACAB007744.
HPA031134.
MIM601254. gene.
neXtProtNX_P52564.
PharmGKBPA30591.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000234206.
HOVERGENHBG108518.
InParanoidP52564.
KOK04433.
OMAESAVAMV.
OrthoDBEOG7J9VPW.
PhylomeDBP52564.

Enzyme and pathway databases

BRENDA2.7.12.2. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_120956. Cellular responses to stress.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkP52564.

Gene expression databases

ArrayExpressP52564.
BgeeP52564.
CleanExHS_MAP2K6.
GenevestigatorP52564.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP52564.
GeneWikiMAP2K6.
GenomeRNAi5608.
NextBio21798.
PMAP-CutDBP52564.
PROP52564.
SOURCESearch...

Entry information

Entry nameMP2K6_HUMAN
AccessionPrimary (citable) accession number: P52564
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM