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Mitogen-activated protein kinase kinase kinase 12
Symbols MAP3K12; DLK; MUK; ZPK; ZPKP1
External IDs OMIM600447 MGI1346881 HomoloGene4592 GeneCards: MAP3K12 Gene
RNA expression pattern
PBB GE MAP3K12 205447 s at tn.png
PBB GE MAP3K12 205448 s at tn.png
More reference expression data
Species Human Mouse
Entrez 7786 26404
Ensembl ENSG00000139625 ENSMUSG00000023050
UniProt Q12852 Q60700
RefSeq (mRNA) NM_006301 NM_009582
RefSeq (protein) NP_006292 NP_033608
Location (UCSC) Chr 12:
52.16 - 52.18 Mb
Chr 15:
102.33 - 102.34 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase kinase kinase 12 is an enzyme that in humans is encoded by the MAP3K12 gene.[1][2]

The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a leucine-zipper domain, and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulated by membrane depolarization via calcineurin. This kinase forms heterodimers with leucine zipper containing transcription factors, such as cAMP responsive element binding protein (CREB) and MYC, and thus may play a regulatory role in PKA or retinoic acid induced neuronal differentiation.[2]


MAP3K12 has been shown to interact with MAPK8IP1,[3] MAP2K7[4] and MAPK8IP2.[3]


  1. ^ Reddy UR, Pleasure D (Aug 1994). "Cloning of a novel putative protein kinase having a leucine zipper domain from human brain". Biochem Biophys Res Commun 202 (1): 613–20. doi:10.1006/bbrc.1994.1972. PMID 8037767.  
  2. ^ a b "Entrez Gene: MAP3K12 mitogen-activated protein kinase kinase kinase 12".  
  3. ^ a b Yasuda, J; Whitmarsh A J, Cavanagh J, Sharma M, Davis R J (Oct. 1999). "The JIP group of mitogen-activated protein kinase scaffold proteins". Mol. Cell. Biol. (UNITED STATES) 19 (10): 7245–54. ISSN 0270-7306. PMID 10490659.  
  4. ^ Merritt, S E; Mata M, Nihalani D, Zhu C, Hu X, Holzman L B (Apr. 1999). "The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate". J. Biol. Chem. (UNITED STATES) 274 (15): 10195–202. ISSN 0021-9258. PMID 10187804.  

Further reading

  • Reddy UR, Nycum L, Slavc I, Biegel JA (1995). "Localization of the human zipper protein kinase gene (ZPK) to chromosome 12q13 by fluorescence in situ hybridization and somatic cell hybrid analysis.". Genomics 25 (2): 597–8. PMID 7790002.  
  • Holzman LB, Merritt SE, Fan G (1995). "Identification, molecular cloning, and characterization of dual leucine zipper bearing kinase. A novel serine/threonine protein kinase that defines a second subfamily of mixed lineage kinases.". J. Biol. Chem. 269 (49): 30808–17. PMID 7983011.  
  • Hirai S, Izawa M, Osada S, et al. (1996). "Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK.". Oncogene 12 (3): 641–50. PMID 8637721.  
  • Mata M, Merritt SE, Fan G, et al. (1996). "Characterization of dual leucine zipper-bearing kinase, a mixed lineage kinase present in synaptic terminals whose phosphorylation state is regulated by membrane depolarization via calcineurin.". J. Biol. Chem. 271 (28): 16888–96. PMID 8663324.  
  • Sakuma H, Ikeda A, Oka S, et al. (1997). "Molecular cloning and functional expression of a cDNA encoding a new member of mixed lineage protein kinase from human brain.". J. Biol. Chem. 272 (45): 28622–9. PMID 9353328.  
  • Merritt SE, Mata M, Nihalani D, et al. (1999). "The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate.". J. Biol. Chem. 274 (15): 10195–202. PMID 10187804.  
  • Reddy UR, Basu A, Bannerman P, et al. (1999). "ZPK inhibits PKA induced transcriptional activation by CREB and blocks retinoic acid induced neuronal differentiation.". Oncogene 18 (31): 4474–84. doi:10.1038/sj.onc.1202813. PMID 10442638.  
  • Douziech M, Laberge G, Grondin G, et al. (1999). "Localization of the mixed-lineage kinase DLK/MUK/ZPK to the Golgi apparatus in NIH 3T3 cells.". J. Histochem. Cytochem. 47 (10): 1287–96. PMID 10490457.  
  • Fukuyama K, Yoshida M, Yamashita A, et al. (2000). "MAPK upstream kinase (MUK)-binding inhibitory protein, a negative regulator of MUK/dual leucine zipper-bearing kinase/leucine zipper protein kinase.". J. Biol. Chem. 275 (28): 21247–54. doi:10.1074/jbc.M001488200. PMID 10801814.  
  • Hébert SS, Daviau A, Grondin G, et al. (2000). "The mixed lineage kinase DLK is oligomerized by tissue transglutaminase during apoptosis.". J. Biol. Chem. 275 (42): 32482–90. doi:10.1074/jbc.M006528200. PMID 10922377.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • 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.  
  • Itoh A, Wang Z, Ito Y, et al. (2004). "SP3 acts as a positive regulator on the core promoter of human ZPK gene.". Biochem. Biophys. Res. Commun. 313 (3): 612–8. PMID 14697235.  
  • Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.  
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.  
  • Graves PR, Winkfield KM, Haystead TA (2005). "Regulation of zipper-interacting protein kinase activity in vitro and in vivo by multisite phosphorylation.". J. Biol. Chem. 280 (10): 9363–74. doi:10.1074/jbc.M412538200. PMID 15611134.  
  • Robitaille H, Proulx R, Robitaille K, et al. (2005). "The mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK) acts as a key regulator of keratinocyte terminal differentiation.". J. Biol. Chem. 280 (13): 12732–41. doi:10.1074/jbc.M411619200. PMID 15695824.  
  • Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome.". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.  


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