MELK

MELK
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4BKY, 4BKZ, 4D2P, 4D2T, 4D2V, 4D2W, 4IXP, 4UMP, 4UMQ, 4UMR, 4UMT, 4UMU, 5IHA, 5IHC, 5IH9, 5IH8
Identifiers
Aliases	MELK, HPK38, maternal embryonic leucine zipper kinase
External IDs	OMIM: 607025 MGI: 106924 HomoloGene: 32111 GeneCards: MELK
EC number	2.7.10.2
Gene location (Human)
Chr.	Chromosome 9 (human)[1]
End	36,677,683 bp[1]
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)[2]
End	44,364,675 bp[2]
RNA expression pattern
	Top expressed in
	secondary oocyte; ; embryo; ; ganglionic eminence; ; amniotic fluid; ; tibia; ; cancellous bone; ; bone marrow; ; cavity of mouth; ; stromal cell of endometrium; ; rectum;
	Top expressed in
	primitive streak; ; abdominal wall; ; dermis; ; ureter; ; endocardial cushion; ; maxillary prominence; ; medial ganglionic eminence; ; right lobe of liver; ; somite; ; Paneth cell;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	transferase activity; nucleotide binding; calcium ion binding; protein kinase activity; non-membrane spanning protein tyrosine kinase activity; kinase activity; protein serine/threonine kinase activity; protein binding; ATP binding; lipid binding;
Cellular component	cytoplasm; membrane; plasma membrane; cell cortex; nucleus;
Biological process	intrinsic apoptotic signaling pathway in response to oxidative stress; hemopoiesis; intracellular signal transduction; phosphorylation; protein phosphorylation; G2/M transition of mitotic cell cycle; neural precursor cell proliferation; positive regulation of apoptotic process; protein autophosphorylation; cell cycle; cell population proliferation; apoptotic process; peptidyl-tyrosine phosphorylation;
	Sources:Amigo / QuickGO
Orthologs
	9833
	17279
	ENSG00000165304
	ENSMUSG00000035683
	Q14680
	Q61846
NM_001256685; NM_001256687; NM_001256688; NM_001256689; NM_001256690;
	NM_001256691; NM_001256692; NM_001256693; NM_014791
	NM_010790
NP_001243614; NP_001243616; NP_001243617; NP_001243618; NP_001243619;
	NP_001243620; NP_001243621; NP_001243622; NP_055606
	NP_034920
	Wikidata
View/Edit Human	View/Edit Mouse

Maternal embryonic leucine zipper kinase (MELK) is an enzyme that in humans is encoded by the MELK gene.[5][6][7] MELK is a serine/threonine kinase belonging to the family of AMPK/Snf1 protein kinases. MELK was first identified present as maternal mRNA in mouse embryos.[8] MELK expression is elevated in a number of cancers and is an active research target for pharmacological inhibition.[9]

MELK was previously believed to be essential for cancer cell proliferation. However, recent research using CRISPR has demonstrated that MELK is fully dispensable for cancer cell growth, casting doubt on the rationale for targeting this protein in patients. The results are dependent on the experimental design. Therefore, there is a need for further research. [10][11][12][13]

Interactions

MELK has been shown to interact with CDC25B.[14]

References

GRCh38: Ensembl release 89: ENSG00000165304 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000035683 - 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.
Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N (February 1996). "Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research. 3 (1): 17–24. doi:10.1093/dnares/3.1.17. PMID 8724849.
Heyer BS, Warsowe J, Solter D, Knowles BB, Ackerman SL (June 1997). "New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo". Molecular Reproduction and Development. 47 (2): 148–56. doi:10.1002/(SICI)1098-2795(199706)47:2<148::AID-MRD4>3.0.CO;2-M. PMID 9136115. S2CID 27882565.
"Entrez Gene: MELK maternal embryonic leucine zipper kinase".
Heyer BS, Kochanowski H, Solter D (August 1999). "Expression of Melk, a new protein kinase, during early mouse development". Developmental Dynamics. 215 (4): 344–51. doi:10.1002/(SICI)1097-0177(199908)215:4<344::AID-AJA6>3.0.CO;2-H. PMID 10417823.
Gray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, et al. (November 2005). "Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers". Cancer Research. 65 (21): 9751–61. doi:10.1158/0008-5472.CAN-04-4531. PMID 16266996.
Lin A, Giuliano CJ, Sayles NM, Sheltzer JM (March 2017). "CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials". eLife. 6. doi:10.7554/eLife.24179. PMC 5365317. PMID 28337968.
Huang HT, Seo HS, Zhang T, Wang Y, Jiang B, Li Q, et al. (September 2017). "MELK is not necessary for the proliferation of basal-like breast cancer cells". eLife. 6. doi:10.7554/eLife.26693. PMC 5605198. PMID 28926338.
Giuliano CJ, Lin A, Smith JC, Palladino AC, Sheltzer JM (February 2018). "MELK expression correlates with tumor mitotic activity but is not required for cancer growth". eLife. 7. doi:10.7554/eLife.32838. PMC 5805410. PMID 29417930.
Settleman J, Sawyers CL, Hunter T (February 2018). "Challenges in validating candidate therapeutic targets in cancer". eLife. 7. doi:10.7554/eLife.32402. PMC 5805407. PMID 29417929.
Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP (October 2002). "Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation". Oncogene. 21 (50): 7630–41. doi:10.1038/sj.onc.1205870. PMID 12400006.

Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T (2007). "Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family". Breast Cancer Research. 9 (1): R17. doi:10.1186/bcr1650. PMC 1851384. PMID 17280616.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
Beullens M, Vancauwenbergh S, Morrice N, Derua R, Ceulemans H, Waelkens E, Bollen M (December 2005). "Substrate specificity and activity regulation of protein kinase MELK". The Journal of Biological Chemistry. 280 (48): 40003–11. doi:10.1074/jbc.M507274200. PMID 16216881.
Vulsteke V, Beullens M, Boudrez A, Keppens S, Van Eynde A, Rider MH, et al. (March 2004). "Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1". The Journal of Biological Chemistry. 279 (10): 8642–7. doi:10.1074/jbc.M311466200. PMID 14699119.
Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP (October 2002). "Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation". Oncogene. 21 (50): 7630–41. doi:10.1038/sj.onc.1205870. PMID 12400006.
Seong HA, Gil M, Kim KT, Kim SJ, Ha H (February 2002). "Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine protein serine/threonine kinase 38 (MPK38)". The Biochemical Journal. 361 (Pt 3): 597–604. doi:10.1042/0264-6021:3610597. PMC 1222342. PMID 11802789.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Gil M, Yang Y, Lee Y, Choi I, Ha H (August 1997). "Cloning and expression of a cDNA encoding a novel protein serine/threonine kinase predominantly expressed in hematopoietic cells". Gene. 195 (2): 295–301. doi:10.1016/S0378-1119(97)00181-9. PMID 9305775.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000165304 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000035683 - 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.

[pmid8724849-5] Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N (February 1996). "Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research. 3 (1): 17–24. doi:10.1093/dnares/3.1.17. PMID 8724849.

[pmid9136115-6] Heyer BS, Warsowe J, Solter D, Knowles BB, Ackerman SL (June 1997). "New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo". Molecular Reproduction and Development. 47 (2): 148–56. doi:10.1002/(SICI)1098-2795(199706)47:2<148::AID-MRD4>3.0.CO;2-M. PMID 9136115. S2CID 27882565.

[entrez-7] "Entrez Gene: MELK maternal embryonic leucine zipper kinase".

[8] Heyer BS, Kochanowski H, Solter D (August 1999). "Expression of Melk, a new protein kinase, during early mouse development". Developmental Dynamics. 215 (4): 344–51. doi:10.1002/(SICI)1097-0177(199908)215:4<344::AID-AJA6>3.0.CO;2-H. PMID 10417823.

[9] Gray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, et al. (November 2005). "Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers". Cancer Research. 65 (21): 9751–61. doi:10.1158/0008-5472.CAN-04-4531. PMID 16266996.

[10] Lin A, Giuliano CJ, Sayles NM, Sheltzer JM (March 2017). "CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials". eLife. 6. doi:10.7554/eLife.24179. PMC 5365317. PMID 28337968.

[11] Huang HT, Seo HS, Zhang T, Wang Y, Jiang B, Li Q, et al. (September 2017). "MELK is not necessary for the proliferation of basal-like breast cancer cells". eLife. 6. doi:10.7554/eLife.26693. PMC 5605198. PMID 28926338.

[12] Giuliano CJ, Lin A, Smith JC, Palladino AC, Sheltzer JM (February 2018). "MELK expression correlates with tumor mitotic activity but is not required for cancer growth". eLife. 7. doi:10.7554/eLife.32838. PMC 5805410. PMID 29417930.

[13] Settleman J, Sawyers CL, Hunter T (February 2018). "Challenges in validating candidate therapeutic targets in cancer". eLife. 7. doi:10.7554/eLife.32402. PMC 5805407. PMID 29417929.

[pmid12400006-14] Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP (October 2002). "Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation". Oncogene. 21 (50): 7630–41. doi:10.1038/sj.onc.1205870. PMID 12400006.

Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Coenzyme 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)

MELK

Interactions

References

Further reading