CPLM-009943

Genbank Nucleotide ID

Dual specificity mitogen-activated protein kinase kinase 6

Protein Synonyms/Alias

MAP kinase kinase 6; MAPKK 6; MAPK/ERK kinase 6; MEK 6; SAPKK3

Mus musculus (Mouse)

Position	Peptide	Type	References
232	INPELNQKGYSVKSD	ubiquitination	[1]

[1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]

Functional Description

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.

DOMAIN 53 314 Protein kinase.
NP_BIND 59 67 ATP (By similarity).
REGION 4 19 D domain (By similarity).
REGION 311 334 DVD domain (By similarity).
ACT_SITE 179 179 Proton acceptor (By similarity).
BINDING 82 82 ATP (By similarity).
MOD_RES 207 207 Phosphoserine; by MAPK3 (Probable).
MOD_RES 211 211 Phosphothreonine; by MAPK3 (Probable).

Apoptosis; ATP-binding; Complete proteome; Cytoplasm; Cytoskeleton; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Stress response; Transcription; Transcription regulation; Transferase; Tyrosine-protein kinase.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
GO:0000187; P:activation of MAPK activity; IDA:MGI.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0060048; P:cardiac muscle contraction; IMP:MGI.
GO:0000165; P:MAPK cascade; IPI:MGI.
GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
GO:0006468; P:protein phosphorylation; IDA:MGI.
GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
GO:0042493; P:response to drug; IEA:Compara.
GO:0006950; P:response to stress; IEA:UniProtKB-KW.
GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.

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.

PS00107; PROTEIN_KINASE_ATP
PS50011; PROTEIN_KINASE_DOM
PS00108; PROTEIN_KINASE_ST