UniProt:P47809 Map2k4

chain
  • initiator methionine:1
  • chain:2-397
checksum B99C6688184E5B3D
comment
  • FUNCTION 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 pro-inflammatory 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.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)ACTIVITY REGULATION Activated in response to a variety of cellular stresses, including UV and gamma-irradiation, heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK.SUBUNIT Interacts with SPAG9. Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14 (By similarity). Interacts (via its DVD domain) with MAP3Ks activators like MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3 (By similarity).INTERACTION Strong expression is detected in most of the central nervous system and in liver and thymus during early stages of development. While expression in nervous system increases over time, expression in fetal liver and thymus gradually decreases as embryogenesis proceeds. High level of expression in the central nervous system persists throughout postnatal development and remained at a stable level in adult brain.DOMAIN The DVD domain (residues 362-385) 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).DOMAIN The D domain (residues 35-50) contains a conserved docking site and is required for the binding to MAPk substrates.PTM Activated by phosphorylation on Ser-255 and Thr-259 by MAP kinase kinase kinases (MAP3Ks).DISRUPTION PHENOTYPE Causes irregular alignment of Purkinje cells in the cerebellum and delayed radial migration in the cortex during brain development. The cardiac-specific deletion prevents pathological cardiac hypertrophy.SIMILARITY Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
crossReference
databaseName UniProt
dbId 95504
description
  • recommendedName: Dual specificity mitogen-activated protein kinase kinase 4 shortName: MAP kinase kinase 4 shortName: MAPKK 4 ecNumber: 2.7.12.2 alternativeName: C-JUN N-terminal kinase kinase 1 shortName: JNK kinase 1 shortName: JNKK 1 alternativeName: JNK-activating kinase 1 alternativeName: MAPK/ERK kinase 4 shortName: MEK 4 alternativeName: SAPK/ERK kinase 1 shortName: SEK1
displayName UniProt:P47809 Map2k4
geneName
  • Map2k4
  • Jnkk1
  • Mek4
  • Mkk4
  • Prkmk4
  • Sek1
  • Serk1
  • Skk1
identifier P47809
isSequenceChanged false
keyword
  • Acetylation
  • Apoptosis
  • ATP-binding
  • Cytoplasm
  • Kinase
  • Methylation
  • Nucleotide-binding
  • Nucleus
  • Phosphoprotein
  • Reference proteome
  • Serine/threonine-protein kinase
  • Stress response
  • Transferase
  • Tyrosine-protein kinase
modified [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType Protein
name
  • Map2k4
otherIdentifier
  • 10387014
  • 111507_at
  • 1426233_at
  • 1451982_at
  • 17264189
  • 26398
  • 4397585
  • 4441080
  • 4443195
  • 4523064
  • 4578768
  • 4594265
  • 4673675
  • 4741847
  • 4958730
  • 5004229
  • 5005913
  • 5040659
  • 5150212
  • 5153123
  • 5154961
  • 5164226
  • 5270667
  • 5318715
  • 5499938
  • 5542069
  • 99960_at
  • A_51_P471440
  • A_55_P2018292
  • A_55_P2098335
  • A_55_P2590349
  • GE33147
  • GO:0000165
  • GO:0000166
  • GO:0003824
  • GO:0004672
  • GO:0004674
  • GO:0004708
  • GO:0004713
  • GO:0005515
  • GO:0005524
  • GO:0005634
  • GO:0005737
  • GO:0005829
  • GO:0006468
  • GO:0006915
  • GO:0009611
  • GO:0016301
  • GO:0016740
  • GO:0033554
  • GO:0034390
  • GO:0035556
  • GO:0036481
  • GO:0043410
  • GO:0071260
  • GO:0106310
  • GO:0140096
  • GO:2000672
  • ILMN_2773179
  • ILMN_2920549
  • U18310_s_at
  • mMC017623
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • MP2K4_MOUSE
sequenceLength 397
species [Species:48892] Mus musculus
stId uniprot:P47809
url http://purl.uniprot.org/uniprot/P47809
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