ZAK

Sterile alpha motif and leucine zipper containing kinase AZK
Identifiers
Symbols	ZAK ; AZK; MLK7; MLT; MLTK; MRK; mlklak; pk
External IDs	OMIM: 609479 MGI: 2443258 HomoloGene: 32331 ChEMBL: 3886 GeneCards: ZAK Gene
EC number	2.7.11.25
Gene ontology Molecular function • magnesium ion binding • protein serine/threonine kinase activity • MAP kinase kinase kinase activity • protein binding • ATP binding • poly(A) RNA binding Cellular component • nucleus • cytoplasm Biological process • cell cycle checkpoint • DNA damage checkpoint • activation of MAPKK activity • protein phosphorylation • response to stress • cytoskeleton organization • cell cycle arrest • activation of JUN kinase activity • cell death • cell proliferation • response to radiation • cell differentiation • intracellular signal transduction • positive regulation of apoptotic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	51776	65964
Ensembl	ENSG00000091436	ENSMUSG00000004085
UniProt	Q9NYL2	Q9ESL4
RefSeq (mRNA)	NM_016653	NM_001164791
RefSeq (protein)	NP_057737	NP_001158263
Location (UCSC)	Chr 2: 173.08 – 173.27 Mb	Chr 2: 72.29 – 72.44 Mb
PubMed search

Sterile alpha motif and leucine zipper containing kinase AZK, also known as ZAK, is a human gene.^[1]

This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[1]

Interactions

ZAK has been shown to interact with ZNF33A.^[2]

References

1. "Entrez Gene: ZAK sterile alpha motif and leucine zipper containing kinase AZK".
2. Yang, Jaw-Ji (Jan 2003). "A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle". Biochem. Biophys. Res. Commun. (United States) 301 (1): 71–7. doi:10.1016/S0006-291X(02)02980-7. ISSN 0006-291X. PMID 12535642.

Further reading

• Liu TC, Huang CJ, Chu YC, et al. (2000). "Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif.". Biochem. Biophys. Res. Commun. 274 (3): 811–6. doi:10.1006/bbrc.2000.3236. PMID 10924358.
• Gotoh I, Adachi M, Nishida E (2001). "Identification and characterization of a novel MAP kinase kinase kinase, MLTK.". J. Biol. Chem. 276 (6): 4276–86. doi:10.1074/jbc.M008595200. PMID 11042189.
• Bloem LJ, Pickard TR, Acton S, et al. (2002). "Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase.". J. Mol. Cell. Cardiol. 33 (9): 1739–50. doi:10.1006/jmcc.2001.1437. PMID 11549352.
• Gross EA, Callow MG, Waldbaum L, et al. (2002). "MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest.". J. Biol. Chem. 277 (16): 13873–82. doi:10.1074/jbc.M111994200. PMID 11836244.
• Yang JJ (2002). "Mixed lineage kinase ZAK utilizing MKK7 and not MKK4 to activate the c-Jun N-terminal kinase and playing a role in the cell arrest.". Biochem. Biophys. Res. Commun. 297 (1): 105–10. doi:10.1016/S0006-291X(02)02123-X. PMID 12220515.
• 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. PMC 139241. PMID 12477932.
• Yang JJ (2003). "A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle.". Biochem. Biophys. Res. Commun. 301 (1): 71–7. doi:10.1016/S0006-291X(02)02980-7. PMID 12535642.
• Takahashi M, Gotoh Y, Isagawa T, et al. (2004). "Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN.". J. Biochem. 133 (2): 181–7. doi:10.1093/jb/mvg022. PMID 12761180.
• 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.
• Cho YY, Bode AM, Mizuno H, et al. (2004). "A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development.". Cancer Res. 64 (11): 3855–64. doi:10.1158/0008-5472.CAN-04-0201. PMID 15172994.
• Jin J, Smith FD, Stark C, et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization.". Curr. Biol. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660.
• Tosti E, Waldbaum L, Warshaw G, et al. (2005). "The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway.". J. Biol. Chem. 279 (46): 47652–60. doi:10.1074/jbc.M409961200. PMID 15342622.
• Huang CY, Kuo WW, Chueh PJ, et al. (2004). "Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK.". Biochem. Biophys. Res. Commun. 324 (1): 424–31. doi:10.1016/j.bbrc.2004.09.067. PMID 15465036.
• Huang CY, Chueh PJ, Tseng CT, et al. (2004). "ZAK re-programs atrial natriuretic factor expression and induces hypertrophic growth in H9c2 cardiomyoblast cells.". Biochem. Biophys. Res. Commun. 324 (3): 973–80. doi:10.1016/j.bbrc.2004.09.156. PMID 15485649.
• 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. PMC 528928. PMID 15489334.
• Choi HS, Choi BY, Cho YY, et al. (2005). "Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-like mitogen-activated protein triple kinase alpha.". J. Biol. Chem. 280 (14): 13545–53. doi:10.1074/jbc.M410521200. PMID 15684425.
• Wang X, Mader MM, Toth JE, et al. (2005). "Complete inhibition of anisomycin and UV radiation but not cytokine induced JNK and p38 activation by an aryl-substituted dihydropyrrolopyrazole quinoline and mixed lineage kinase 7 small interfering RNA.". J. Biol. Chem. 280 (19): 19298–305. doi:10.1074/jbc.M413059200. PMID 15737997.
• Benzinger A, Muster N, Koch HB, et al. (2005). "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer.". Mol. Cell Proteomics 4 (6): 785–95. doi:10.1074/mcp.M500021-MCP200. PMID 15778465.
• Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4.". Nature 434 (7034): 724–31. doi:10.1038/nature03466. PMID 15815621.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.