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] Band 9p13.2 Start 36,572,862 bp [1] End 36,677,683 bp [1]
Gene location (Mouse) Chr. Chromosome 4 (mouse) [2] Band 4 B1|4 23.46 cM Start 44,300,876 bp [2] End 44,364,675 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) 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 BioGPS 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 Species Human Mouse Entrez 9833 17279 Ensembl ENSG00000165304 ENSMUSG00000035683 UniProt Q14680 Q61846 RefSeq (mRNA) NM_001256685 NM_001256687 NM_001256688 NM_001256689 NM_001256690 NM_001256691 NM_001256692 NM_001256693 NM_014791 NM_010790 RefSeq (protein) NP_001243614 NP_001243616 NP_001243617 NP_001243618 NP_001243619 NP_001243620 NP_001243621 NP_001243622 NP_055606 NP_034920 Location (UCSC) Chr 9: 36.57 – 36.68 Mb Chr 4: 44.3 – 44.36 Mb PubMed search [3] [4]
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

1. GRCh38: Ensembl release 89: ENSG00000165304 - Ensembl, May 2017
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.
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.
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.
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.
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.

Further reading

• 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.