UniProt Accession

 MP2K4_MOUSE; P47809 

Genbank Protein ID

 U18310 

Genbank Nucleotide ID

 AAB81554.1 

Protein Name

 Dual specificity mitogen-activated protein kinase kinase 4 

Protein Synonyms/Alias

 MAP kinase kinase 4; MAPKK 4; C-JUN N-terminal kinase kinase 1; JNK kinase 1; JNKK 1; JNK-activating kinase 1; MAPK/ERK kinase 4; MEK 4; SAPK/ERK kinase 1; SEK1 

Gene Name

 Map2k4 

Gene Synonyms/Alias

 Jnkk1; Mek4; Mkk4; Prkmk4; Sek1; Serk1; Skk1 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
52	NFANPPVKSTARFTL	ubiquitination	[1]

Reference

 [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. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. 

Sequence Annotation

 DOMAIN 100 366 Protein kinase.
 NP_BIND 106 114 ATP (By similarity).
 REGION 35 50 D domain (By similarity).
 REGION 362 385 DVD domain (By similarity).
 ACT_SITE 227 227 Proton acceptor (By similarity).
 BINDING 129 129 ATP.
 MOD_RES 2 2 N-acetylalanine (By similarity).
 MOD_RES 88 88 Phosphoserine (By similarity).
 MOD_RES 255 255 Phosphoserine; by MAP3K (By similarity).
 MOD_RES 259 259 Phosphothreonine; by MAP3K (By  

Keyword

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

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 397 AA 

Protein Sequence

Gene Ontology

 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:0007257; P:activation of JUN kinase activity; ISO:MGI.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0071260; P:cellular response to mechanical stimulus; IEA:Compara. 

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. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS