MELK
Developmental stage
Increases during G2/M phase compared to interphase. Protein level decreases when cells exit mitosis, probably due to degradation.
Domain
The KA1 domain mediates binding to phospholipids and targeting to membranes.
Function
Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.
Involvement in disease
Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.
Post-translational modifications
Autophosphorylated: autophosphorylation of the T-loop at Thr-167 and Ser-171 is required for activation. Thr-478 phosphorylation during mitosis promotes interaction with PPP1R8 (Probable).
Sequence Similarities
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
Tissue Specificity
Expressed in placenta, kidney, thymus, testis, ovary and intestine.
Cellular localization
- Cell membrane
- Peripheral membrane protein
Alternative names
KIAA0175, MELK, Maternal embryonic leucine zipper kinase, hMELK, Protein kinase Eg3, Protein kinase PK38, Tyrosine-protein kinase MELK, pEg3 kinase, hPK38