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MAP3K11
Identifiers
Aliases	MAP3K11, MEKK11, MLK-3, MLK3, PTK1, SPRK, mitogen-activated protein kinase kinase kinase 11
External IDs	OMIM: 600050; MGI: 1346880; HomoloGene: 37618; GeneCards: MAP3K11; OMA:MAP3K11 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q13.1 Start 65,597,756 bp End 65,615,382 bp
Gene location (Mouse) Chr. Chromosome 19 (mouse) Band 19 A|19 4.34 cM Start 5,738,770 bp End 5,752,893 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve granulocyte apex of heart mucosa of transverse colon right lobe of liver monocyte right lung spleen C1 segment upper lobe of left lung Top expressed in granulocyte yolk sac lip external carotid artery internal carotid artery intestinal villus right kidney thymus crypt of lieberkuhn of small intestine zygote More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein homodimerization activity mitogen-activated protein kinase kinase kinase binding kinase activity protein binding identical protein binding mitogen-activated protein kinase kinase binding ATP binding MAP kinase kinase kinase activity protein serine/threonine kinase activity protein kinase activity JUN kinase kinase kinase activity protein tyrosine kinase activity Cellular component centrosome membrane microtubule organizing center microtubule cytoskeleton cytoplasm intracellular anatomical structure Biological process phosphorylation positive regulation of JUN kinase activity cell death positive regulation of JNK cascade positive regulation of neuron apoptotic process microtubule-based process cell population proliferation protein autophosphorylation JNK cascade protein phosphorylation positive regulation of apoptotic process MAPK cascade peptidyl-tyrosine phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4296 26403 Ensembl ENSG00000173327 ENSMUSG00000004054 UniProt Q16584 Q80XI6 RefSeq (mRNA) NM_002419 NM_022012 RefSeq (protein) NP_002410 NP_002410.1 NP_071295 Location (UCSC) Chr 11: 65.6 – 65.62 Mb Chr 19: 5.74 – 5.75 Mb PubMed search
Wikidata
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Mitogen-activated protein kinase kinase kinase 11 is an enzyme that in humans is encoded by the MAP3K11 gene.

Function

The protein encoded by this gene is called MLK3 and it is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates JNK and p38, and is found to be involved in the transcription activity of AP1 mediated by Rho family GTPases and CDC42.

Interactions

MAP3K11 has been shown to interact with:

• AKT1,
• CDC42,
• MAPK8IP1,
• MAPK8IP2, and
• SH3RF1.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000173327 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000004054 – 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. Smith CM, Ma NS, Nowak NJ, Shows TB, Gerhard DS (October 1997). "A 3-Mb Contig from D11S987 to MLK3, a Gene-Rich Region in 11q13". Genome Res. 7 (8): 835–42. doi:10.1101/gr.7.8.835. PMC 310665. PMID 9267807.
6. Ing YL, Leung IW, Heng HH, Tsui LC, Lassam NJ (June 1994). "MLK-3: identification of a widely-expressed protein kinase bearing an SH3 domain and a leucine zipper-basic region domain". Oncogene. 9 (6): 1745–50. PMID 8183572.
7. Kant S, Swat W, Zhang S, Zhang ZY, Neel BG, Flavell RA, Davis RJ (Oct 1, 2011). "TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway". Genes Dev. 25 (19): 2069–78. doi:10.1101/gad.17224711. PMC 3197205. PMID 21979919.
8. "Entrez Gene: MAP3K11 mitogen-activated protein kinase kinase kinase 11".
9. Barthwal MK, Sathyanarayana P, Kundu CN, Rana B, Pradeep A, Sharma C, Woodgett JR, Rana A (February 2003). "Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival". J. Biol. Chem. 278 (6): 3897–902. doi:10.1074/jbc.M211598200. PMID 12458207.
10. Nagata Ki, Puls A, Futter C, Aspenstrom P, Schaefer E, Nakata T, Hirokawa N, Hall A (January 1998). "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3". EMBO J. 17 (1): 149–58. doi:10.1093/emboj/17.1.149. PMC 1170366. PMID 9427749.
11. Böck BC, Vacratsis PO, Qamirani E, Gallo KA (May 2000). "Cdc42-induced activation of the mixed-lineage kinase SPRK in vivo. Requirement of the Cdc42/Rac interactive binding motif and changes in phosphorylation". J. Biol. Chem. 275 (19): 14231–41. doi:10.1074/jbc.275.19.14231. PMID 10799501.
12. ^ Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ (October 1999). "The JIP group of mitogen-activated protein kinase scaffold proteins". Mol. Cell. Biol. 19 (10): 7245–54. doi:10.1128/mcb.19.10.7245. PMC 84717. PMID 10490659.
13. Figueroa C, Tarras S, Taylor J, Vojtek AB (November 2003). "Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex". J. Biol. Chem. 278 (48): 47922–7. doi:10.1074/jbc.M307357200. PMID 14504284.

Further reading

• van de Bovenkamp M, Nottet HS, Pereira CF (2003). "Interactions of human immunodeficiency virus-1 proteins with neurons: possible role in the development of human immunodeficiency virus-1-associated dementia". Eur. J. Clin. Invest. 32 (8): 619–27. doi:10.1046/j.1365-2362.2002.01029.x. PMID 12190962. S2CID 37260932.
• 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.
• Gallo KA, Mark MR, Scadden DT, Wang Z, Gu Q, Godowski PJ (1994). "Identification and characterization of SPRK, a novel src-homology 3 domain-containing proline-rich kinase with serine/threonine kinase activity". J. Biol. Chem. 269 (21): 15092–100. doi:10.1016/S0021-9258(17)36578-X. PMID 8195146.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (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.
• Tanaka S, Hanafusa H (1998). "Guanine-nucleotide exchange protein C3G activates JNK1 by a ras-independent mechanism. JNK1 activation inhibited by kinase negative forms of MLK3 and DLK mixed lineage kinases". J. Biol. Chem. 273 (3): 1281–4. doi:10.1074/jbc.273.3.1281. PMID 9430657.
• Leung IW, Lassam N (1999). "Dimerization via tandem leucine zippers is essential for the activation of the mitogen-activated protein kinase kinase kinase, MLK-3". J. Biol. Chem. 273 (49): 32408–15. doi:10.1074/jbc.273.49.32408. PMID 9829970.
• Merritt SE, Mata M, Nihalani D, Zhu C, Hu X, Holzman LB (1999). "The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate". J. Biol. Chem. 274 (15): 10195–202. doi:10.1074/jbc.274.15.10195. PMID 10187804.
• Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ (2000). "The JIP Group of Mitogen-Activated Protein Kinase Scaffold Proteins". Mol. Cell. Biol. 19 (10): 7245–54. doi:10.1128/mcb.19.10.7245. PMC 84717. PMID 10490659.
• Kelkar N, Gupta S, Dickens M, Davis RJ (2000). "Interaction of a Mitogen-Activated Protein Kinase Signaling Module with the Neuronal Protein JIP3". Mol. Cell. Biol. 20 (3): 1030–43. doi:10.1128/MCB.20.3.1030-1043.2000. PMC 85220. PMID 10629060.
• Hehner SP, Hofmann TG, Ushmorov A, Dienz O, Wing-Lan Leung I, Lassam N, Scheidereit C, Dröge W, Schmitz ML (2000). "Mixed-Lineage Kinase 3 Delivers CD3/CD28-Derived Signals into the IκB Kinase Complex". Mol. Cell. Biol. 20 (7): 2556–68. doi:10.1128/MCB.20.7.2556-2568.2000. PMC 85472. PMID 10713178.
• Böck BC, Vacratsis PO, Qamirani E, Gallo KA (2000). "Cdc42-induced activation of the mixed-lineage kinase SPRK in vivo. Requirement of the Cdc42/Rac interactive binding motif and changes in phosphorylation". J. Biol. Chem. 275 (19): 14231–41. doi:10.1074/jbc.275.19.14231. PMID 10799501.
• Leung IW, Lassam N (2001). "The kinase activation loop is the key to mixed lineage kinase-3 activation via both autophosphorylation and hematopoietic progenitor kinase 1 phosphorylation". J. Biol. Chem. 276 (3): 1961–7. doi:10.1074/jbc.M004092200. PMID 11053428.
• Svensson AC, Raudsepp T, Larsson C, Di Cristofano A, Chowdhary B, La Mantia G, Rask L, Andersson G (2001). "Chromosomal distribution, localization and expression of the human endogenous retrovirus ERV9". Cytogenet. Cell Genet. 92 (1–2): 89–96. doi:10.1159/000056875. PMID 11306803. S2CID 19266745.
• Zhang H, Gallo KA (2002). "Autoinhibition of mixed lineage kinase 3 through its Src homology 3 domain". J. Biol. Chem. 276 (49): 45598–603. doi:10.1074/jbc.M107176200. PMID 11590155.
• Lambert JM, Karnoub AE, Graves LM, Campbell SL, Der CJ (2002). "Role of MLK3-mediated activation of p70 S6 kinase in Rac1 transformation". J. Biol. Chem. 277 (7): 4770–7. doi:10.1074/jbc.M109379200. PMID 11713255.
• Chadee DN, Yuasa T, Kyriakis JM (2002). "Direct Activation of Mitogen-Activated Protein Kinase Kinase Kinase MEKK1 by the Ste20p Homologue GCK and the Adapter Protein TRAF2". Mol. Cell. Biol. 22 (3): 737–49. doi:10.1128/MCB.22.3.737-749.2002. PMC 133545. PMID 11784851.
• Vacratsis PO, Phinney BS, Gage DA, Gallo KA (2002). "Identification of in vivo phosphorylation sites of MLK3 by mass spectrometry and phosphopeptide mapping". Biochemistry. 41 (17): 5613–24. CiteSeerX 10.1.1.381.6228. doi:10.1021/bi016075c. PMID 11969422.

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