MAP3K10

Mitogen-activated protein kinase kinase kinase 10 is an enzyme that in humans is encoded by the MAP3K10 gene.[5][6][7]

MAP3K10
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2RF0
Identifiers
Aliases	MAP3K10, MEKK10, MLK2, MST, mitogen-activated protein kinase kinase kinase 10
External IDs	OMIM: 600137 MGI: 1346879 HomoloGene: 1834 GeneCards: MAP3K10
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.2 Start 40,191,426 bp[1] End 40,215,575 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 A3 Start 27,656,375 bp[2] End 27,674,598 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • protein kinase activity • nucleotide binding • protein homodimerization activity • GO:0001106 transcription corepressor activity • kinase activity • protein serine/threonine kinase activity • bHLH transcription factor binding • ATP binding • MAP kinase kinase kinase activity • JUN kinase kinase kinase activity Cellular component • cytoplasm • intracellular Biological process • phosphorylation • activation of MAPKK activity • positive regulation of JUN kinase activity • cell death • positive regulation of JNK cascade • negative regulation of sequence-specific DNA binding transcription factor activity • protein phosphorylation • JNK cascade • peptidyl-serine phosphorylation • autophosphorylation • smoothened signaling pathway • peptidyl-threonine phosphorylation • negative regulation of transcription, DNA-templated • signal transduction • apoptotic process • activation of JNKK activity • activation of JUN kinase activity • positive regulation of apoptotic process • MAPK cascade Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4294	269881
Ensembl	ENSG00000130758	ENSMUSG00000040390
UniProt	Q02779	Q66L42
RefSeq (mRNA)	NM_002446	NM_001081292 NM_001290528
RefSeq (protein)	NP_002437	NP_001277457
Location (UCSC)	Chr 19: 40.19 – 40.22 Mb	Chr 7: 27.66 – 27.67 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phosphorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis.[7]

Interactions

MAP3K10 has been shown to interact with:

• CDC42,[8]
• Huntingtin,[9]
• KIF3A,[8]
• MAPK8IP1,[10]
• MAPK8IP2,[10] and
• NEUROD1.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000130758 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040390 - 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. Dorow DS, Devereux L, Tu GF, Price G, Nicholl JK, Sutherland GR, Simpson RJ (February 1996). "Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2". Eur J Biochem. 234 (2): 492–500. doi:10.1111/j.1432-1033.1995.492_b.x. PMID 8536694.
6. Katoh M, Hirai M, Sugimura T, Terada M (May 1995). "Cloning and characterization of MST, a novel (putative) serine/threonine kinase with SH3 domain". Oncogene. 10 (7): 1447–51. PMID 7731697.
7. "Entrez Gene: MAP3K10 mitogen-activated protein kinase kinase kinase 10".
8. 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.
9. Liu YF, Dorow D, Marshall J (June 2000). "Activation of MLK2-mediated signaling cascades by polyglutamine-expanded huntingtin". J. Biol. Chem. 275 (25): 19035–40. doi:10.1074/jbc.C000180200. PMID 10801775.
10. 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.
11. Marcora E, Gowan K, Lee JE (August 2003). "Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2". Proc. Natl. Acad. Sci. U.S.A. 100 (16): 9578–83. doi:10.1073/pnas.1133382100. PMC 170960. PMID 12881483.

Further reading

• 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. PMID 8195146.
• Dorow DS, Devereux L, Dietzsch E, De Kretser T (1993). "Identification of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domains". Eur. J. Biochem. 213 (2): 701–10. doi:10.1111/j.1432-1033.1993.tb17810.x. PMID 8477742.
• Hirai Si, Katoh M, Terada M, Kyriakis JM, Zon LI, Rana A, Avruch J, Ohno S (1997). "MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase". J. Biol. Chem. 272 (24): 15167–73. doi:10.1074/jbc.272.24.15167. PMID 9182538.
• Hirai Si, Noda K, Moriguchi T, Nishida E, Yamashita A, Deyama T, Fukuyama K, Ohno S (1998). "Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2". J. Biol. Chem. 273 (13): 7406–12. doi:10.1074/jbc.273.13.7406. PMID 9516438.
• Rasmussen RK, Ji H, Eddes JS, Moritz RL, Reid GE, Simpson RJ, Dorow DS (1998). "Two-dimensional electrophoretic analysis of mixed lineage kinase 2 N-terminal domain binding proteins". Electrophoresis. 19 (5): 809–17. doi:10.1002/elps.1150190535. PMID 9629920. S2CID 21204230.
• Rasmussen RK, Rusak J, Price G, Robinson PJ, Simpson RJ, Dorow DS (1998). "Mixed-lineage kinase 2-SH3 domain binds dynamin and greatly enhances activation of GTPase by phospholipid". Biochem. J. 335 (Pt 1): 119–24. doi:10.1042/bj3350119. PMC 1219759. PMID 9742220.
• Liu YF, Dorow D, Marshall J (2000). "Activation of MLK2-mediated signaling cascades by polyglutamine-expanded huntingtin". J. Biol. Chem. 275 (25): 19035–40. doi:10.1074/jbc.C000180200. PMID 10801775.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Savinainen A, Garcia EP, Dorow D, Marshall J, Liu YF (2001). "Kainate receptor activation induces mixed lineage kinase-mediated cellular signaling cascades via post-synaptic density protein 95". J. Biol. Chem. 276 (14): 11382–6. doi:10.1074/jbc.M100190200. PMID 11152698.
• Xu Z, Maroney AC, Dobrzanski P, Kukekov NV, Greene LA (2001). "The MLK Family Mediates c-Jun N-Terminal Kinase Activation in Neuronal Apoptosis". Mol. Cell. Biol. 21 (14): 4713–24. doi:10.1128/MCB.21.14.4713-4724.2001. PMC 87148. PMID 11416147.
• Poy MN, Yang Y, Rezaei K, Fernström MA, Lee AD, Kido Y, Erickson SK, Najjar SM (2002). "CEACAM1 regulates insulin clearance in liver". Nat. Genet. 30 (3): 270–6. doi:10.1038/ng840. PMID 11850617. S2CID 30473455.
• Akbarzadeh S, Ji H, Frecklington D, Marmy-Conus N, Mok YF, Bowes L, Devereux L, Linsenmeyer M, Simpson RJ, Dorow DS (2002). "Mixed lineage kinase 2 interacts with clathrin and influences clathrin-coated vesicle trafficking". J. Biol. Chem. 277 (39): 36280–7. doi:10.1074/jbc.M204626200. PMID 12105200.
• Figueroa C, Tarras S, Taylor J, Vojtek AB (2004). "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.
• Eckey M, Tenbaum SP, Muñoz A, Baniahmad A (2004). "Mixed lineage kinase 2 enhances trans-repression of Alien and nuclear receptors". Mol. Cell. Endocrinol. 213 (1): 71–8. doi:10.1016/j.mce.2003.10.035. PMID 15062575. S2CID 38167719.
• Jaffe AB, Hall A, Schmidt A (2005). "Association of CNK1 with Rho guanine nucleotide exchange factors controls signaling specificity downstream of Rho". Curr. Biol. 15 (5): 405–12. doi:10.1016/j.cub.2004.12.082. PMID 15753034. S2CID 16479940.
• Kollers S, Musilova P, Rubes J, Rocha D (2007). "Comparative mapping reveals multiple rearrangements between pig chromosome 6 and human 19q13". Anim. Genet. 37 (6): 595–6. doi:10.1111/j.1365-2052.2006.01516.x. PMID 17121608.