MELK - Maternal embryonic leucine zipper kinase - human protein (Function)
 
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MELK »  Maternal embryonic leucine zipper kinase   [ EC 2.7.11.1 ]
 
Protein also known as:  Tyrosine-protein kinase MELK [EC 2.7.10.2].
Gene name:  MELK
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
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  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
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  • UniProtKB KW
Calcium ion bindingdefinition[GO:0005509]  
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Lipid bindingdefinition[GO:0008289]  
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  • UniProtKB KW
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
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  • UniProtKB
Protein bindingdefinition[GO:0005515]  
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  • IntAct
  • UniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
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GO biological process 
Apoptotic processdefinition[GO:0006915]  
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Cell proliferationdefinition[GO:0008283]  
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  • UniProtKB
G2/M transition of mitotic cell cycledefinition[GO:0000086]  
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  • UniProtKB
Hemopoiesisdefinition[GO:0030097]  
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  • Ortholog Curator
Intracellular signal transductiondefinition[GO:0035556]  
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  • RefGenome
Intrinsic apoptotic signaling pathway in response to oxidative stressdefinition[GO:0008631] silver  
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  • Ortholog Compara
Neural precursor cell proliferationdefinition[GO:0061351]  
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  • Ortholog Curator
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
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  • GOC
  • EC 2 GO
Positive regulation of apoptotic processdefinition[GO:0043065]  
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  • Ortholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
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  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
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  • PROSITE-ProRule
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
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  • UniProtKB
It is regulated in the following manner
Activated by autophosphorylation of the T-loop at Thr-167 and Ser-171: in contrast to other members of the SNF1 subfamily, phosphorylation at Thr-167 is not mediated by STK11/LKB1 but via autophosphorylation instead. Inhibited by calcium-binding. Kinase activity is also regulated by reducing agents: dithiothreitol (DTT) or reduced glutathione are required for kinase activity in vitro; such dependence is however not due to the presence of disulfide bonds.  
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  • UniProtKB
Note 
Potential therapeutic target for treatment of somatic tumors, such as brain and breast cancers, down-regulation of MELK inhibiting tumorigenesis (PubMed17960622, PubMed20861186).  
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  • UniProtKB
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Cell cycle  definition   [KW-0131]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MELK
GenomeRNAi: 9833
PRO: PR:Q14680
Chemistry
GuidetoPHARMACOLOGY: 2102