P52564 (MP2K6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	334 AA.
Sequence status	Complete.
Protein existence	Evidence 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.20 Ref.25
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.24
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. Ref.11 Ref.19 Ref.28
Subcellular location	Nucleus. Cytoplasm. Cytoplasm › cytoskeleton. 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.24
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.21 The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates By similarity. Ref.21
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.22 Ref.24 Acetylation of Ser-207 and Thr-211 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
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 process	Apoptosis Stress response Transcription Transcription regulation
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage induced protein phosphorylation Traceable author statement PubMed 10848581. Source: ProtInc MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell cycle arrest Traceable author statement PubMed 10848581. Source: ProtInc innate immune response Traceable author statement. Source: Reactome muscle cell differentiation Traceable author statement. Source: Reactome nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome positive regulation of muscle cell differentiation Traceable author statement. Source: Reactome regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW stress-activated MAPK cascade Traceable author statement. Source: Reactome toll-like receptor 1 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 transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase activity Traceable author statement PubMed 10848581. Source: ProtInc protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LRRK2	Q5S007	4	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 334

334

Dual specificity mitogen-activated protein kinase kinase 6

PRO_0000086386

Regions

Domain

53 – 314

262

Protein kinase

Nucleotide binding

59 – 67

9

ATP By similarity

Region

4 – 19

16

D domain By similarity

Region

311 – 334

24

DVD domain

Sites

Active site

179

1

Proton acceptor By similarity

Binding site

82

1

ATP By similarity

Site

14 – 15

2

Cleavage; by anthrax lethal factor

Amino acid modifications

Modified residue

207

1

O-acetylserine; by Yersinia yopJ; alternate

Modified residue

207

1

Phosphoserine; by MAP3K; alternate Ref.22

Modified residue

211

1

O-acetylthreonine; by Yersinia yopJ; alternate

Modified residue

211

1

Phosphothreonine; by MAP3K; alternate Ref.22

Natural variations

Alternative sequence

1 – 56

56

Missing in isoform 2.

VSP_004882

Experimental info

Mutagenesis

207

1

S → A: Inactivation.

Mutagenesis

207

1

S → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.

Mutagenesis

211

1

T → A: Inactivation.

Mutagenesis

211

1

T → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.

Sequence conflict

125

1

V → M in AAB03705. Ref.3

Sequence conflict

125

1

V → M in AAB03708. Ref.3

Secondary structure

1

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334

Helix Strand Turn

Details...

Helix

50 – 52

3

Beta strand

53 – 61

9

Beta strand

63 – 72

10

Turn

73 – 76

4

Beta strand

77 – 84

8

Helix

90 – 104

15

Turn

110 – 112

3

Beta strand

115 – 120

6

Beta strand

122 – 130

9

Beta strand

133 – 135

3

Helix

136 – 145

10

Helix

152 – 172

21

Helix

182 – 184

3

Beta strand

185 – 187

3

Beta strand

193 – 195

3

Helix

201 – 203

3

Helix

207 – 212

6

Helix

222 – 225

4

Helix

236 – 252

17

Helix

263 – 272

10

Turn

280 – 282

3

Helix

285 – 294

10

Helix

299 – 301

3

Helix

305 – 308

4

Helix

312 – 319

8

Helix

324 – 332

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MKK6b) [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 4ECA8014522216AF	FASTA	334	37,492
	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
	Isoform 2 (MKK6) [UniParc]. Checksum: 1EE7FC1B26B11AE4	FASTA	278	31,339
	10 20 30 40 50 60 MELGRGAYGV VEKMRHVPSG QIMAVKRIRA TVNSQEQKRL LMDLDISMRT VDCPFTVTFY 70 80 90 100 110 120 GALFREGDVW ICMELMDTSL DKFYKQVIDK GQTIPEDILG KIAVSIVKAL EHLHSKLSVI 130 140 150 160 170 180 HRDVKPSNVL INALGQVKMC DFGISGYLVD SVAKTIDAGC KPYMAPERIN PELNQKGYSV 190 200 210 220 230 240 KSDIWSLGIT MIELAILRFP YDSWGTPFQQ LKQVVEEPSP QLPADKFSAE FVDFTSQCLK 250 260 270 KNSKERPTYP ELMQHPFFTL HESKGTDVAS FVKLILGD

References

	« Hide 'large scale' referencesShow '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]	"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.
[20]	"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.
[21]	"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.
[22]	"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, MASS SPECTROMETRY.
[23]	"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.
[24]	"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: MASS SPECTROMETRY, PHOSPHORYLATION BY MAP3K5/ASK1, ENZYME REGULATION.
[25]	"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.
[26]	"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.
[27]	"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].
[28]	"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.
[29]	"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.

IPI

IPI00003814.
IPI00219569.

PIR

S71631.

RefSeq

NP_002749.2. NM_002758.3.

UniGene

Hs.463978.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P52564.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31346N.

IntAct

P52564. 7 interactions.

MINT

MINT-3019559.

STRING

9606.ENSP00000351997.

PTM databases

PhosphoSite

P52564.

Polymorphism databases

DMDM

1709088.

Proteomic databases

PaxDb

P52564.

PRIDE

P52564.

Protocols and materials databases

DNASU

5608.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000589647; ENSP00000467213; ENSG00000108984.
ENST00000590474; ENSP00000468348; ENSG00000108984.

GeneID

5608.

KEGG

hsa:5608.

UCSC

uc002jii.3. human.

Organism-specific databases

CTD

5608.

GeneCards

GC17P067410.

HGNC

HGNC:6846. MAP2K6.

HPA

CAB007744.
HPA031134.

MIM

601254. gene.

neXtProt

NX_P52564.

PharmGKB

PA30591.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000234206.

HOVERGEN

HBG108518.

InParanoid

P52564.

KO

K04433.

OMA

ESAVAMV.

OrthoDB

EOG4P2Q2M.

PhylomeDB

P52564.

Enzyme and pathway databases

BRENDA

2.7.12.2. 2681.

Pathway_Interaction_DB

anthraxpathway. Cellular roles of Anthrax toxin.
il1pathway. IL1-mediated signaling events.
il12_2pathway. IL12-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
p38_mkk3_6pathway. p38 MAPK signaling pathway.
ar_tf_pathway. Regulation of Androgen receptor activity.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.
p38gammadeltapathway. Signaling mediated by p38-gamma and p38-delta.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.

Reactome

REACT_111045. Developmental Biology.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P52564.

Bgee

P52564.

CleanEx

HS_MAP2K6.

Genevestigator

P52564.

GermOnline

ENSG00000108984. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P52564.

ChEMBL

CHEMBL2171.

EvolutionaryTrace

P52564.

GenomeRNAi

5608.

NextBio

21798.

PMAP-CutDB

P52564.

SOURCE

Search...

Entry information

Entry name

MP2K6_HUMAN

Accession

Primary (citable) accession number: P52564

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 135 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.