ZAK

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; OMA:MAP3K20 - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	173,268,015 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	72,272,954 bp
RNA expression pattern
	Top expressed in
	right ventricle; ; Skeletal muscle tissue of rectus abdominis; ; biceps brachii; ; Skeletal muscle tissue of biceps brachii; ; body of tongue; ; saphenous vein; ; tail of epididymis; ; vena cava; ; urethra; ; seminal vesicula;
	Top expressed in
	interventricular septum; ; temporal muscle; ; ankle; ; triceps brachii muscle; ; digastric muscle; ; extraocular muscle; ; sternocleidomastoid muscle; ; soleus muscle; ; atrioventricular valve; ; intercostal muscle;
	More reference expression data
	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; protein binding; MAP kinase kinase kinase activity; ATP binding; magnesium ion binding; RNA binding;
Cellular component	nucleus; cytoplasm; cytosol;
Biological process	cell differentiation; intracellular signal transduction; cell cycle checkpoint signaling; phosphorylation; DNA damage checkpoint signaling; response to stress; cell death; protein phosphorylation; cytoskeleton organization; positive regulation of apoptotic process; cell cycle; response to radiation; cell population proliferation; embryonic digit morphogenesis; limb development; mitotic cell cycle checkpoint signaling; stress-activated MAPK cascade; cellular response to gamma radiation;
	Sources:Amigo / QuickGO
Orthologs
	51776
	65964
	ENSG00000091436
	ENSMUSG00000004085
	Q9NYL2
	Q9ESL4
	NM_016653; NM_133646
	NM_001164791; NM_023057; NM_178084
	NP_057737; NP_598407
	NP_001158263; NP_075544; NP_835185
	Wikidata
View/Edit Human	View/Edit Mouse

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

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000091436 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000004085 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: ZAK sterile alpha motif and leucine zipper containing kinase AZK".
^ Liu TC, Huang CJ, Chu YC, Wei CC, Chou CC, Chou MY, et al. (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.
^ Yang JJ (Jan 2003). "A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle". Biochemical and Biophysical Research Communications. 301 (1): 71–77. doi:10.1016/S0006-291X(02)02980-7. ISSN 0006-291X. PMID 12535642.

Lee JS, Lin YY, Wang TS, Liu JY, Lin WW, Yang JJ (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. PMID 29374956.
Liu TC, Huang CJ, Chu YC, Wei CC, Chou CC, Chou MY, et al. (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.
Gotoh I, Adachi M, Nishida E (2001). "Identification and characterization of a novel MAP kinase kinase kinase, MLTK". Journal of Biological Chemistry. 276 (6): 4276–4286. doi:10.1074/jbc.M008595200. PMID 11042189.
Bloem LJ, Pickard TR, Acton S, Donoghue M, Beavis RC, Knierman MD, et al. (2002). "Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase". Journal of Molecular and Cellular Cardiology. 33 (9): 1739–1750. doi:10.1006/jmcc.2001.1437. PMID 11549352.
Gross EA, Callow MG, Waldbaum L, Thomas S, Ruggieri R (2002). "MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest". Journal of Biological Chemistry. 277 (16): 13873–13882. 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". Biochemical and Biophysical Research Communications. 297 (1): 105–110. doi:10.1016/S0006-291X(02)02123-X. PMID 12220515.
Yang JJ (2003). "A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle". Biochemical and Biophysical Research Communications. 301 (1): 71–77. doi:10.1016/S0006-291X(02)02980-7. PMID 12535642.
Takahashi M, Gotoh Y, Isagawa T, Nishimura T, Goyama E, Kim HS, et al. (2004). "Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN". Journal of Biochemistry. 133 (2): 181–187. doi:10.1093/jb/mvg022. PMID 12761180.
Cho YY, Bode AM, Mizuno H, Choi BY, Choi HS, Dong Z (2004). "A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development". Cancer Research. 64 (11): 3855–3864. doi:10.1158/0008-5472.CAN-04-0201. PMID 15172994.
Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Current Biology. 14 (16): 1436–1450. doi:10.1016/j.cub.2004.07.051. PMID 15324660. S2CID 2371325.
Tosti E, Waldbaum L, Warshaw G, Gross EA, Ruggieri R (2005). "The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway". Journal of Biological Chemistry. 279 (46): 47652–47660. doi:10.1074/jbc.M409961200. PMID 15342622.
Huang CY, Kuo WW, Chueh PJ, Tseng CT, Chou MY, Yang JJ (2004). "Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK". Biochemical and Biophysical Research Communications. 324 (1): 424–431. doi:10.1016/j.bbrc.2004.09.067. PMID 15465036.
Huang CY, Chueh PJ, Tseng CT, Liu KY, Tsai HY, Kuo WW, et al. (2004). "ZAK re-programs atrial natriuretic factor expression and induces hypertrophic growth in H9c2 cardiomyoblast cells". Biochemical and Biophysical Research Communications. 324 (3): 973–980. doi:10.1016/j.bbrc.2004.09.156. PMID 15485649.
Choi HS, Choi BY, Cho YY, Zhu F, Bode AM, Dong Z (2005). "Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-like mitogen-activated protein triple kinase alpha". Journal of Biological Chemistry. 280 (14): 13545–13553. doi:10.1074/jbc.M410521200. PMID 15684425.
Wang X, Mader MM, Toth JE, Yu X, Jin N, Campbell RM, 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". Journal of Biological Chemistry. 280 (19): 19298–19305. doi:10.1074/jbc.M413059200. PMID 15737997.
Benzinger A, Muster N, Koch HB, Yates JR 3rd, Hermeking H (2005). "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer". Molecular & Cellular Proteomics. 4 (6): 785–795. doi:10.1074/mcp.M500021-MCP200. PMID 15778465.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000091436 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[entrez-5] "Entrez Gene: ZAK sterile alpha motif and leucine zipper containing kinase AZK".

[6] Liu TC, Huang CJ, Chu YC, Wei CC, Chou CC, Chou MY, et al. (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.

[pmid12535642-7] Yang JJ (Jan 2003). "A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle". Biochemical and Biophysical Research Communications. 301 (1): 71–77. doi:10.1016/S0006-291X(02)02980-7. ISSN 0006-291X. PMID 12535642.

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Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Interactions

References

Further reading