Q5E9X2 (MP2K6_BOVIN) 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

Gene names

Name:

MAP2K6

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	334 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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 By similarity.
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 By similarity. 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 By similarity.
Subunit structure	Dimer By similarity. 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 By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Note: Binds to microtubules By similarity.
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 By similarity. The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates By similarity.
Post-translational modification	Weakly autophosphorylated By similarity. 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 By similarity.
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
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW 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...

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_0000248967
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 By similarity
Sites
	Active site	179	1	Proton acceptor By similarity
	Binding site	82	1	ATP By similarity
Amino acid modifications
	Modified residue	27	1	Phosphoserine By similarity
	Modified residue	28	1	Phosphothreonine By similarity
	Modified residue	82	1	N6-acetyllysine By similarity
	Modified residue	207	1	Phosphoserine; by MAPK3 By similarity
	Modified residue	211	1	Phosphothreonine; by MAPK3 By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q5E9X2 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: 39C23E5541719C04	FASTA	334	37,578
	10 20 30 40 50 60 MSQSKGKKRN PGLKIPKEAF EQPQTSSTPP RDLDSKACIS IGNQNFEVKA DDLEPIVELG 70 80 90 100 110 120 RGAYGVVEKM RHVPSEQIMA 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 DKFSEEFVDF TSQCLKKNSK 310 320 330 ERPTYPELMQ HPFFTLHESK ATDVASFVKS ILGD

References

[1]	"Characterization of 954 bovine full-CDS cDNA sequences." Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L. BMC Genomics 6:166-166(2005) [PubMed: 16305752] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	BT020798 mRNA. Translation: AAX08815.1.
IPI	IPI00690263.
RefSeq	NP_001029217.1. NM_001034045.1.
UniGene	Bt.561.
3D structure databases
HSSP	HSSP built from PDB template 1S9I based on UniProtKB P36507.
ProteinModelPortal	Q5E9X2.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5E9X2.
Proteomic databases
PRIDE	Q5E9X2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000002115; ENSBTAP00000002115; ENSBTAG00000001609.
GeneID	286883.
KEGG	bta:286883.
Organism-specific databases
CTD	5608.
Phylogenomic databases
GeneTree	ENSGT00570000078767.
HOVERGEN	HBG108518.
InParanoid	Q5E9X2.
OrthoDB	EOG4P2Q2M.
PhylomeDB	Q5E9X2.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K04433.
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...

Entry information

Entry name

MP2K6_BOVIN

Accession

Primary (citable) accession number: Q5E9X2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	March 15, 2005
Last modified:	December 14, 2011
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program