MELK

Protein-coding gene in the species Homo sapiens
MELK
Available structures
PDBOrtholog 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
AliasesMELK, HPK38, maternal embryonic leucine zipper kinase
External IDsOMIM: 607025; MGI: 106924; HomoloGene: 32111; GeneCards: MELK; OMA:MELK - orthologs
EC number2.7.10.2
Gene location (Human)
Chromosome 9 (human)
Chr.Chromosome 9 (human)[1]
Chromosome 9 (human)
Genomic location for MELK
Genomic location for MELK
Band9p13.2Start36,572,862 bp[1]
End36,677,683 bp[1]
Gene location (Mouse)
Chromosome 4 (mouse)
Chr.Chromosome 4 (mouse)[2]
Chromosome 4 (mouse)
Genomic location for MELK
Genomic location for MELK
Band4 B1|4 23.46 cMStart44,300,876 bp[2]
End44,364,675 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • secondary oocyte

  • embryo

  • ganglionic eminence

  • amniotic fluid

  • tibia

  • trabecular bone

  • bone marrow

  • oral cavity

  • 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
SpeciesHumanMouse
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 MbChr 4: 44.3 – 44.36 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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. ^ a b c GRCh38: Ensembl release 89: ENSG00000165304 – Ensembl, May 2017
  2. ^ a b c 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.
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Non-specific serine/threonine protein kinases (EC 2.7.11.1)
Pyruvate dehydrogenase kinase (EC 2.7.11.2)
Dephospho-(reductase kinase) kinase (EC 2.7.11.3)
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)
(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)
(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)
Myosin-heavy-chain kinase (EC 2.7.11.7)
Fas-activated serine/threonine kinase (EC 2.7.11.8)
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)
  • -
IκB kinase (EC 2.7.11.10)
cAMP-dependent protein kinase (EC 2.7.11.11)
cGMP-dependent protein kinase (EC 2.7.11.12)
Protein kinase C (EC 2.7.11.13)
Rhodopsin kinase (EC 2.7.11.14)
Beta adrenergic receptor kinase (EC 2.7.11.15)
G-protein coupled receptor kinases (EC 2.7.11.16)
Ca2+/calmodulin-dependent (EC 2.7.11.17)
Myosin light-chain kinase (EC 2.7.11.18)
Phosphorylase kinase (EC 2.7.11.19)
Elongation factor 2 kinase (EC 2.7.11.20)
Polo kinase (EC 2.7.11.21)
Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)
Polo kinase (EC 2.7.11.21)
Cyclin-dependent kinase (EC 2.7.11.22)
(RNA-polymerase)-subunit kinase (EC 2.7.11.23)
Mitogen-activated protein kinase (EC 2.7.11.24)
MAP3K (EC 2.7.11.25)
Tau-protein kinase (EC 2.7.11.26)
(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)
  • -
Tropomyosin kinase (EC 2.7.11.28)
  • -
Low-density-lipoprotein receptor kinase (EC 2.7.11.29)
  • -
Receptor protein serine/threonine kinase (EC 2.7.11.30)
MAP2K
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