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Protein MAP2K4 PDB 3ALN.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesMAP2K4, JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4, SAPKK-1, SAPKK1, SEK1, SERK1, SKK1, mitogen-activated protein kinase kinase 4
External IDsMGI: 1346869 HomoloGene: 48159 GeneCards: MAP2K4
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for MAP2K4
Genomic location for MAP2K4
Band17p12Start12,020,824 bp[1]
End12,143,830 bp[1]
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 17: 12.02 – 12.14 MbChr 11: 65.69 – 65.79 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Dual specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.[5]

This gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK1. This kinase is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as in the organogenesis of liver.[6]


MAP2K4 has been shown to interact with FLNC,[7] MAPK8,[8][9][10][11][12] MAPK8IP3[13][14] and AKT1.[9]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000065559 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033352 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M (May 1995). "Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2". Science. 268 (5208): 286–90. Bibcode:1995Sci...268..286L. doi:10.1126/science.7716521. PMID 7716521.
  6. ^ "Entrez Gene: MAP2K4 mitogen-activated protein kinase kinase 4".
  7. ^ Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; Kyriakis J M; Avruch J (January 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. UNITED STATES. 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. ISSN 0021-9258. PMID 9006895.
  8. ^ Lee, Clement M; Onésime Djamila; Reddy C Damodara; Dhanasekaran N; Reddy E Premkumar (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. United States. 99 (22): 14189–94. Bibcode:2002PNAS...9914189L. doi:10.1073/pnas.232310199. ISSN 0027-8424. PMC 137859. PMID 12391307.
  9. ^ a b Park, Hee-Sae; Kim Mi-Sung; Huh Sung-Ho; Park Jihyun; Chung Jongkyeong; Kang Sang Sun; Choi Eui-Ju (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem. United States. 277 (4): 2573–8. doi:10.1074/jbc.M110299200. ISSN 0021-9258. PMID 11707464.
  10. ^ Chen, Z; Cobb M H (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. United States. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. ISSN 0021-9258. PMID 11279118.
  11. ^ Tournier, C; Whitmarsh A J; Cavanagh J; Barrett T; Davis R J (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. UNITED STATES. 94 (14): 7337–42. Bibcode:1997PNAS...94.7337T. doi:10.1073/pnas.94.14.7337. ISSN 0027-8424. PMC 23822. PMID 9207092.
  12. ^ Cheng, J; Yang J; Xia Y; Karin M; Su B (April 2000). "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Mol. Cell. Biol. UNITED STATES. 20 (7): 2334–42. doi:10.1128/MCB.20.7.2334-2342.2000. ISSN 0270-7306. PMC 85399. PMID 10713157.
  13. ^ Ito, M; Yoshioka K; Akechi M; Yamashita S; Takamatsu N; Sugiyama K; Hibi M; Nakabeppu Y; Shiba T; Yamamoto K I (November 1999). "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". Mol. Cell. Biol. UNITED STATES. 19 (11): 7539–48. doi:10.1128/mcb.19.11.7539. ISSN 0270-7306. PMC 84763. PMID 10523642.
  14. ^ Matsuura, Hiroshi; Nishitoh Hideki; Takeda Kohsuke; Matsuzawa Atsushi; Amagasa Teruo; Ito Michihiko; Yoshioka Katsuji; Ichijo Hidenori (October 2002). "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade". J. Biol. Chem. United States. 277 (43): 40703–9. doi:10.1074/jbc.M202004200. ISSN 0021-9258. PMID 12189133.

Further reading[edit]