Dual specificity mitogen-activated protein kinase kinase 4

NameDual specificity mitogen-activated protein kinase kinase 4
Synonyms
  • 2.7.12.2
  • c-Jun N-terminal kinase kinase 1
  • JNK-activating kinase 1
  • JNKK
  • JNKK1
  • MAP kinase kinase 4
  • MAPK/ERK kinase 4
  • MEK 4
  • MEK4
  • MKK4
  • PRKMK4
  • SAPK kinase 1
  • SAPK/ERK kinase 1
  • SAPKK-1
  • SAPKK1
  • SEK1
  • SERK1
  • SKK1
  • Stress-activated protein kinase kinase 1
Gene NameMAP2K4
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009089|Dual specificity mitogen-activated protein kinase kinase 4
MAAPSPSGGGGSGGGSGSGTPGPVGSPAPGHPAVSSMQGKRKALKLNFANPPFKSTARFT
LNPNPTGVQNPHIERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMV
HKPSGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMEL
MSTSFDKFYKYVYSVLDDVIPEEILGKITLATVKALNHLKENLKIIHRDIKPSNILLDRS
GNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYEL
ATGRFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKE
LLKHPFILMYEERAVEVACYVCKILDQMPATPSSPMYVD
Number of residues399
Molecular Weight44287.34
Theoretical pINot Available
GO Classification
Functions
  • ATP binding
  • protein kinase activity
  • protein serine/threonine kinase activity
  • protein tyrosine kinase activity
Processes
  • toll-like receptor 10 signaling pathway
  • toll-like receptor 2 signaling pathway
  • signal transduction
  • toll-like receptor 3 signaling pathway
  • toll-like receptor 4 signaling pathway
  • toll-like receptor 5 signaling pathway
  • toll-like receptor 9 signaling pathway
  • toll-like receptor signaling pathway
  • toll-like receptor TLR1
  • innate immune response
  • toll-like receptor TLR6
  • Fc-epsilon receptor signaling pathway
  • TRIF-dependent toll-like receptor signaling pathway
  • cellular response to mechanical stimulus
  • apoptotic process
  • JNK cascade
  • MyD88-dependent toll-like receptor signaling pathway
  • MyD88-independent toll-like receptor signaling pathway
  • stress-activated MAPK cascade
Components
  • nucleus
  • cytosol
General FunctionProtein tyrosine kinase activity
Specific FunctionDual 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP45985
UniProtKB Entry NameMP2K4_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0017683|Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)
ATGGCGGCTCCGAGCCCGAGCGGCGGCGGCGGCTCCGGGGGCGGCAGCGGCAGCGGCACC
CCCGGCCCCGTAGGGTCCCCGGCGCCAGGCCACCCGGCCGTCAGCAGCATGCAGGGCTTT
CAGATAAACTTCTGTGAAAAGGCACAAAGTAAACGCAAAGCACTGAAGTTGAATTTTGCA
AATCCACCTTTCAAATCTACAGCAAGGTTTACTCTGAATCCCAATCCTACAGGAGTTCAA
AACCCACACATAGAGAGACTGAGAACACACAGCATTGAGTCATCAGGAAAACTGAAGATC
TCCCCTGAACAACACTGGGATTTCACTGCAGAGGACTTGAAAGACCTTGGAGAAATTGGA
CGAGGAGCTTATGGTTCTGTCAACAAAATGGTCCACAAACCAAGTGGGCAAATAATGGCA
GTTAAAAGAATTCGGTCAACAGTGGATGAAAAAGAACAAAAACAACTTCTTATGGATTTG
GATGTAGTAATGCGGAGTAGTGATTGCCCATACATTGTTCAGTTTTATGGTGCACTCTTC
AGAGAGGGTGACTGTTGGATCTGTATGGAACTCATGTCTACCTCGTTTGATAAGTTTTAC
AAATATGTATATAGTGTATTAGATGATGTTATTCCAGAAGAAATTTTAGGCAAAATCACT
TTAGCAACTGTGAAAGCACTAAACCACTTAAAAGAAAACTTGAAAATTATTCACAGAGAT
ATCAAACCTTCCAATATTCTTCTGGACAGAAGTGGAAATATTAAGCTCTGTGACTTCGGC
ATCAGTGGACAGCTTGTGGACTCTATTGCCAAGACAAGAGATGCTGGCTGTAGGCCATAC
ATGGCACCTGAAAGAATAGACCCAAGCGCATCACGACAAGGATATGATGTCCGCTCTGAT
GTCTGGAGTTTGGGGATCACATTGTATGAGTTGGCCACAGGCCGATTTCCTTATCCAAAG
TGGAATAGTGTATTTGATCAACTAACACAAGTCGTGAAAGGAGATCCTCCGCAGCTGAGT
AATTCTGAGGAAAGGGAATTCTCCCCGAGTTTCATCAACTTTGTCAACTTGTGCCTTACG
AAGGATGAATCCAAAAGGCCAAAGTATAAAGAGCTTCTGAAACATCCCTTTATTTTGATG
TATGAAGAACGTGCCGTTGAGGTCGCATGCTATGTTTGTAAAATCCTGGATCAAATGCCA
GCTACTCCCAGCTCTCCCATGTATGTCGATTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:6844
Chromosome Location17
LocusNot Available
References
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