MAP2K4

MAP2K4
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3ALN, 3ALO, 3VUT
Identifiers
Aliases	MAP2K4, JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4, SAPKK-1, SAPKK1, SEK1, SERK1, SKK1, mitogen-activated protein kinase kinase 4
External IDs	OMIM: 601335 MGI: 1346869 HomoloGene: 48159 GeneCards: MAP2K4
Gene location (Human)
Chr.	Chromosome 17 (human)[1]
End	12,143,830 bp[1]
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)[2]
End	65,788,297 bp[2]
Gene ontology
Molecular function	• transferase activity; • protein kinase activity; • nucleotide binding; • kinase activity; • GO:0001948 protein binding; • protein tyrosine kinase activity; • ATP binding; • MAP kinase kinase activity; • JUN kinase kinase activity; • protein serine/threonine kinase activity; • mitogen-activated protein kinase kinase kinase binding;
Cellular component	• cytoplasm; • cell nucleus; • dendrite cytoplasm; • cytosol; • perikaryon; • axon;
Biological process	• phosphorylation; • MAPK cascade; • protein phosphorylation; • cellular response to mechanical stimulus; • response to wounding; • peptidyl-tyrosine phosphorylation; • signal transduction; • negative regulation of motor neuron apoptotic process; • apoptotic process; • cell growth involved in cardiac muscle cell development; • cellular response to sorbitol; • positive regulation of smooth muscle cell apoptotic process; • JNK cascade; • positive regulation of protein phosphorylation; • positive regulation of neuron apoptotic process; • positive regulation of DNA replication; • activation of JUN kinase activity; • positive regulation of apoptotic process; • positive regulation of nitric-oxide synthase biosynthetic process; • regulation of mitotic cell cycle; • signal transduction by protein phosphorylation; • stress-activated protein kinase signaling cascade; • activation of protein kinase activity; • regulation of apoptotic process; • activation of MAPK activity; • Fc-epsilon receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	6416
	26398
	ENSG00000065559
	ENSMUSG00000033352
	P45985
	P47809
	NM_001281435; NM_003010
NM_009157; NM_001316367; NM_001316368; NM_001316369; NM_001362739;
	NM_001362740
	NP_001268364; NP_003001
NP_001303296; NP_001303297; NP_001303298; NP_033183; NP_001349668;
	NP_001349669
	Wikidata
View/Edit Human	View/Edit Mouse

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

MAP2K4 encodes a dual-specificity kinase that belongs to the Ser/Thr protein kinase family. MAP2K4 phosphorylates MAP kinases in response to various environmental stresses or mitogenic stimuli. MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38 are substrates for MAP2K4, but MAPK1/ERK2 and MAPK3/ERK1 are not phosphorylated by MAP2K4. MAP2K4 is phosphorylated and activated by MAP3K1/MEKK1. Knockout mouse studies suggest roles for MAP2K4 in mediating T cell development and liver organogenesis.[6]

Interactions

MAP2K4 has been shown to interact with:

gollark: MIT-licensed, you can fork it.

gollark: Look, the main code is all right here, other stuff is... well, it's spread across a lot of files, but you can see it, check the `local files = whatever` bit and my pastebin account.

gollark: https://pastebin.com/RM13UGFa

gollark: I'm not saying much about the *other* exploit, because that would provide clues about it.

gollark: There are issues I know of in GPS (pretty obvious, hard to exploit, hard to patch), rednet repeaters (not useful to exploit, easy to patch, not too obvious), rednet itself (obvious, easily exploitable, but most people making serious programs are already aware), potatOS (very non-obvious, not a huge issue as accidental RCE still isn't possible, easy to exploit if you know how).

References

GRCh38: Ensembl release 89: ENSG00000065559 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000033352 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
"Entrez Gene: MAP2K4 mitogen-activated protein kinase kinase 4".
Xia Y, Wu Z, Su B, Murray B, Karin M (November 1998). "JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension". Genes & Development. 21 (21): 3369–81. doi:10.1101/gad.12.21.3369. PMID 9808624.
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.
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.
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.
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.
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.
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.
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.
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.

Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

MAP2K4

Interactions

References

Further reading