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MAP2K3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1LEZ
Identifiers
Aliases	MAP2K3, MAPKK3, MEK3, MKK3, PRKMK3, SAPKK-2, SAPKK2, mitogen-activated protein kinase kinase 3
External IDs	OMIM: 602315; MGI: 1346868; HomoloGene: 56430; GeneCards: MAP2K3; OMA:MAP2K3 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17p11.2 Start 21,284,672 bp End 21,315,232 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 B2 Start 60,822,859 bp End 60,843,637 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell vena cava blood body of tongue saphenous vein mucosa of pharynx pylorus superior surface of tongue cardia monocyte Top expressed in temporal muscle sternocleidomastoid muscle ankle digastric muscle triceps brachii muscle muscle of thigh fetal liver hematopoietic progenitor cell lip esophagus vastus lateralis muscle More reference expression data BioGPS n/a
Gene ontology Molecular function ATP binding protein tyrosine kinase activity protein kinase activity protein binding kinase activity nucleotide binding transferase activity MAP kinase kinase activity protein kinase binding protein serine/threonine kinase activity Cellular component nucleoplasm cytosol membrane cytoplasm Biological process MAPK cascade protein phosphorylation positive regulation of transcription, DNA-templated peptidyl-tyrosine phosphorylation phosphorylation signal transduction positive regulation of protein kinase activity inflammatory response cardiac muscle contraction regulation of mitotic cell cycle stress-activated protein kinase signaling cascade activation of protein kinase activity regulation of apoptotic process cellular response to vascular endothelial growth factor stimulus p38MAPK cascade positive regulation of blood vessel endothelial cell migration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5606 26397 Ensembl ENSG00000034152 ENSMUSG00000018932 UniProt P46734 O09110 RefSeq (mRNA) NM_002756 NM_145109 NM_145110 NM_001316332 NM_008928 RefSeq (protein) NP_001303261 NP_002747 NP_659731 NP_032954 Location (UCSC) Chr 17: 21.28 – 21.32 Mb Chr 11: 60.82 – 60.84 Mb PubMed search
Wikidata
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Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the MAP2K3 gene.

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersinia pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene.

Interactions

MAP2K3 has been shown to interact with TAOK2 and PLCB2.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000034152 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000018932 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (Mar 1998). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenet Cell Genet. 78 (3–4): 301–3. doi:10.1159/000134677. hdl:11577/2469645. PMID 9465908.
6. "Entrez Gene: MAP2K3 mitogen-activated protein kinase kinase 3".
7. Chen, Z; Cobb M H (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. ISSN 0021-9258. PMID 11279118.
8. Barr, Alastair J; Marjoram Robin; Xu Jing; Snyderman Ralph (Apr 2002). "Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3". Biochem. Biophys. Res. Commun. 293 (1): 647–52. doi:10.1016/S0006-291X(02)00259-0. ISSN 0006-291X. PMID 12054652.

Further reading

• Ben-Levy R, Hooper S, Wilson R, et al. (1999). "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2". Curr. Biol. 8 (19): 1049–57. doi:10.1016/S0960-9822(98)70442-7. PMID 9768359. S2CID 15627349.
• Doza YN, Cuenda A, Thomas GM, et al. (1995). "Activation of the MAP kinase homologue RK requires the phosphorylation of Thr-180 and Tyr-182 and both residues are phosphorylated in chemically stressed KB cells". FEBS Lett. 364 (2): 223–8. Bibcode:1995FEBSL.364..223D. doi:10.1016/0014-5793(95)00346-B. PMID 7750576. S2CID 25025858.
• Dérijard B, Raingeaud J, Barrett T, et al. (1995). "Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms". Science. 267 (5198): 682–5. Bibcode:1995Sci...267..682D. doi:10.1126/science.7839144. PMID 7839144. S2CID 9153074.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Zheng CF, Guan KL (1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. 268 (32): 23933–9. doi:10.1016/S0021-9258(20)80474-8. PMID 8226933.
• Raingeaud J, Whitmarsh AJ, Barrett T, et al. (1996). "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway". Mol. Cell. Biol. 16 (3): 1247–55. doi:10.1128/mcb.16.3.1247. PMC 231107. PMID 8622669.
• Stein B, Brady H, Yang MX, et al. (1996). "Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade". J. Biol. Chem. 271 (19): 11427–33. doi:10.1074/jbc.271.19.11427. PMID 8626699.
• Moriguchi T, Toyoshima F, Gotoh Y, et al. (1996). "Purification and identification of a major activator for p38 from osmotically shocked cells. Activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2". J. Biol. Chem. 271 (43): 26981–8. doi:10.1074/jbc.271.43.26981. PMID 8900184.
• Han J, Wang X, Jiang Y, et al. (1997). "Identification and characterization of a predominant isoform of human MKK3". FEBS Lett. 403 (1): 19–22. Bibcode:1997FEBSL.403...19H. doi:10.1016/S0014-5793(97)00021-5. PMID 9038352. S2CID 5714052.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Hutchison M, Berman KS, Cobb MH (1998). "Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades". J. Biol. Chem. 273 (44): 28625–32. doi:10.1074/jbc.273.44.28625. PMID 9786855.
• Chan-Hui PY, Weaver R (1999). "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades". Biochem. J. 336 (Pt 3): 599–609. doi:10.1042/bj3360599. PMC 1219910. PMID 9841871.
• Chen Z, Hutchison M, Cobb MH (1999). "Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain". J. Biol. Chem. 274 (40): 28803–7. doi:10.1074/jbc.274.40.28803. PMID 10497253.
• Kurata S (2000). "Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress". J. Biol. Chem. 275 (31): 23413–6. doi:10.1074/jbc.C000308200. PMID 10856288.
• Majka M, Ratajczak J, Kowalska MA, Ratajczak MZ (2000). "Binding of stromal derived factor-1alpha (SDF-1alpha) to CXCR4 chemokine receptor in normal human megakaryoblasts but not in platelets induces phosphorylation of mitogen-activated protein kinase p42/44 (MAPK), ELK-1 transcription factor and serine/threonine kinase AKT". Eur. J. Haematol. 64 (3): 164–72. doi:10.1034/j.1600-0609.2000.90112.x. PMID 10997882. S2CID 207549349.
• Fleming Y, Armstrong CG, Morrice N, et al. (2001). "Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7". Biochem. J. 352 Pt 1 (Pt 1): 145–54. doi:10.1042/0264-6021:3520145. PMC 1221441. PMID 11062067.
• Venter JC, Adams MD, Myers EW, et al. (2001). "The sequence of the human genome". Science. 291 (5507): 1304–51. Bibcode:2001Sci...291.1304V. doi:10.1126/science.1058040. PMID 11181995.
• Chen Z, Cobb MH (2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.

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