MELK (Maternal Embryonic Leucine Zipper Kinase)
A serine/threonine-protein kinase involved in cell cycle regulation, stem cell self-renewal, and oncogenic signaling.
Gene Information Card
| Symbol | MELK |
|---|---|
| Full Name | Maternal Embryonic Leucine Zipper Kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 9p13.2 |
| NCBI Gene ID | 9833 ncbi.nlm.nih.gov/gene/9833 |
| Ensembl ID | ENSG00000165304 |
| UniProt ID | Q14680 |
| OMIM ID | 607025 |
| HGNC ID | 16870 |
| Aliases | HPK38, KIAA0175, pEg3 |
Description
MELK (Maternal Embryonic Leucine Zipper Kinase) is a serine/threonine-protein kinase that plays a critical role in cell cycle progression, particularly during mitosis, and is involved in stem cell self-renewal and survival. It is overexpressed in various cancers and is considered a potential therapeutic target. The gene encodes a protein containing a kinase domain and a leucine zipper motif, which mediates protein-protein interactions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Overexpression of MELK promotes cell proliferation and resistance to apoptosis via activation of the PI3K/AKT pathway. | High expression correlates with poor prognosis (PMID: 26921324). |
| Glioblastoma | MELK is upregulated in glioma stem cells and supports tumor growth by phosphorylating Bcl-2 family members to inhibit apoptosis. | Functional studies in cell lines and xenografts (PMID: 23934111). |
| Colorectal Cancer | MELK enhances Wnt/β-catenin signaling, driving tumorigenesis and metastasis. | Gene expression and knockdown experiments (PMID: 28411370). |
| Prostate Cancer | MELK overexpression is associated with castration-resistant prostate cancer and promotes cell cycle progression. | Clinical sample analysis and in vitro assays (PMID: 29367600). |
| Acute Myeloid Leukemia | MELK is highly expressed in leukemic stem cells and contributes to chemoresistance. | Patient cohort data and functional studies (PMID: 27895058). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone Marrow | 8.7 | Low |
| Brain | 6.3 | Low |
| Breast | 4.1 | Low |
| Colon | 3.5 | Low |
| Lung | 2.8 | Low |
| Liver | 1.9 | Not detected |
| Heart | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (Breast cancer) | 12.5 | High expression; associated with proliferation |
| U87MG (Glioblastoma) | 18.3 | Very high; linked to stemness |
| HCT116 (Colorectal cancer) | 9.8 | Moderate; promotes Wnt signaling |
| PC3 (Prostate cancer) | 14.1 | High; castration-resistant phenotype |
| K562 (Leukemia) | 7.2 | Moderate; chemoresistance role |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.1% | Unknown; rare germline variant (ClinVar) |
| c.1342G>A (p.Glu448Lys) | Missense | <0.1% | Unknown; rare somatic (COSMIC) |
| c.1720A>G (p.Asn574Asp) | Missense | <0.1% | Unknown; rare somatic (COSMIC) |
| c.1960_1961insA (p.Thr654Asnfs*2) | Frameshift | <0.1% | Loss of function; rare (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Thr654Asnfs*2) are predicted to truncate the protein, likely resulting in loss of kinase activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations have been reported in MELK.
Dominant Negative (DN)
No dominant-negative mutations have been described for MELK.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0004674 (serine/threonine kinase activity) |
| • GO:0005524 (ATP binding) | • GO:0006468 (protein phosphorylation) |
| • GO:0007049 (cell cycle) | • GO:0051301 (cell division) |
| • GO:0019901 (protein kinase binding) | • GO:0043066 (negative regulation of apoptotic process) |
Pathways
• PI3K/AKT signaling pathway
• Wnt/β-catenin signaling pathway
• Cell cycle - mitosis
• Apoptosis regulation
Protein Summary
MELK is a 651-amino acid serine/threonine-protein kinase with a central kinase domain and a C-terminal leucine zipper motif. It localizes to the nucleus and cytoplasm and is involved in cell cycle regulation, particularly during mitosis. MELK phosphorylates multiple substrates including Bcl-2 family members (e.g., Bcl-G), CDC25B, and ZPR1, thereby modulating cell survival, proliferation, and stem cell self-renewal. Its overexpression in various cancers and stem cell populations makes it an attractive target for small-molecule inhibitors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MELK Knockout HEK293 Cell Line | EDJ-KQ3665 | Human | 9833 | Details Get a Quote |
| MELK Knockout A-549 Cell Line | EDJ-KQ25646 | Human | 9833 | Details Get a Quote |
| MELK Knockout HCT 116 Cell Line | EDJ-KQ25647 | Human | 9833 | Details Get a Quote |
| MELK Knockout HeLa Cell Line | EDJ-KQ25648 | Human | 9833 | Details Get a Quote |
| MELK Knockout HAP1 Cell Line | EDC08204 | Human | 9833 | Details Get a Quote |
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