ZAK

Sterile alpha motif and leucine zipper containing kinase AZK, also known as ZAK, is a human gene.[5]

MAP3K20
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5HES
Identifiers
Aliases	MAP3K20, AZK, MLK7, MLT, MLTK, MRK, mlklak, pk, ZAK, SFMMP, sterile alpha motif and leucine zipper containing kinase AZK, mitogen-activated protein kinase kinase kinase 20, MLTKalpha, MLTKbeta, CNM6
External IDs	OMIM: 609479 MGI: 2443258 HomoloGene: 32331 GeneCards: MAP3K20
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q31.1 Start 173,075,435 bp[1] End 173,268,015 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 C3 Start 72,285,637 bp[2] End 72,442,610 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • nucleotide binding • protein kinase activity • metal ion binding • kinase activity • protein serine/threonine kinase activity • GO:0001948 protein binding • MAP kinase kinase kinase activity • ATP binding • magnesium ion binding • RNA binding Cellular component • cell nucleus • cytoplasm • cytosol Biological process • cell differentiation • GO:0007243 intracellular signal transduction • cell cycle checkpoint • activation of JUN kinase activity • phosphorylation • activation of MAPKK activity • DNA damage checkpoint • response to stress • cell death • protein phosphorylation • cytoskeleton organization • cell cycle arrest • positive regulation of apoptotic process • cell cycle • response to radiation • cellular proliferation • embryonic digit morphogenesis • limb development • mitotic cell cycle checkpoint • stress-activated MAPK cascade • cellular response to gamma radiation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	51776	65964
Ensembl	ENSG00000091436	ENSMUSG00000004085
UniProt	Q9NYL2	Q9ESL4
RefSeq (mRNA)	NM_016653 NM_133646	NM_001164791 NM_023057 NM_178084
RefSeq (protein)	NP_057737 NP_598407	NP_001158263 NP_075544 NP_835185
Location (UCSC)	Chr 2: 173.08 – 173.27 Mb	Chr 2: 72.29 – 72.44 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[5] [6]

Interactions

ZAK has been shown to interact with ZNF33A.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000091436 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000004085 - 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. "Entrez Gene: ZAK sterile alpha motif and leucine zipper containing kinase AZK".
6. Liu, Te-Chung; Huang, Chang-Jen; Chu, Yu-Chuan; Wei, Chih-Chang; Chou, Chun-Chieh; Chou, Ming-Yung; Chou, Chen-Kung; Yang, Jaw-Ji (11 August 2000). "Cloning and Expression of ZAK, a Mixed Lineage Kinase-like Protein Containing a Leucine-Zipper and a Sterile-Alpha Motif". Biochemical and Biophysical Research Communications. 274 (3): 811–816. doi:10.1006/bbrc.2000.3236. PMID 10924358.
7. 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. 301 (1): 71–7. doi:10.1016/S0006-291X(02)02980-7. ISSN 0006-291X. PMID 12535642.

• Lee, Jin-Sun (28 February 2018). "Antitumorigenic Effects of ZAKβ, an Alternative Splicing Isoform of ZAK". The Chinese Journal of Physiology. 61 (1): 25–34. doi:10.4077/CJP.2018.BAG528.

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. Bibcode:2002PNAS...9916899M. 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. Bibcode:2005Natur.434..724H. 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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.