Names & Taxonomy
- Uniprot ID:
- Q14680
- Entry Name:
- MELK_HUMAN
- Status:
- reviewed
- Protein Names:
- Maternal embryonic leucine zipper kinase (hMELK) (EC 2.7.11.1) (Protein kinase Eg3) (pEg3 kinase) (Protein kinase PK38) (hPK38) (Tyrosine-protein kinase MELK) (EC 2.7.10.2)
- Gene Names:
- MELK KIAA0175
- Gene Names Primary:
- MELK
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 651
- Sequence:
- MKDYDELLKYYELHETIGTGGFAKVKLACHILTGEMVAIKIMDKNTLGSDLPRIKTEIEALKNLRHQHICQLYHVLETANKIFMVLEYCPGGELFDYIISQDRLSEEETRVVFRQIVSAVAYVHSQGYAHRDLKPENLLFDEYHKLKLIDFGLCAKPKGNKDYHLQTCCGSLAYAAPELIQGKSYLGSEADVWSMGILLYVLMCGFLPFDDDNVMALYKKIMRGKYDVPKWLSPSSILLLQQMLQVDPKKRISMKNLLNHPWIMQDYNYPVEWQSKNPFIHLDDDCVTELSVHHRNNRQTMEDLISLWQYDHLTATYLLLLAKKARGKPVRLRLSSFSCGQASATPFTDIKSNNWSLEDVTASDKNYVAGLIDYDWCEDDLSTGAATPRTSQFTKYWTESNGVESKSLTPALCRTPANKLKNKENVYTPKSAVKNEEYFMFPEPKTPVNKNQHKREILTTPNRYTTPSKARNQCLKETPIKIPVNSTGTDKLMTGVISPERRCRSVELDLNQAHMEETPKRKGAKVFGSLERGLDKVITVLTRSKRKGSARDGPRRLKLHYNVTTTRLVNPDQLLNEIMSILPKKHVDFVQKGYTLKCQTQSDFGKVTMQFELEVCQLQKPDVVGIRRQRLKGDAWVYKRLVEDILSSCKV
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane
Function
- 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.
- Catalytic Activity:
- ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
- Enzyme Regulation:
- ENZYME REGULATION: 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.
- Active Site:
- ACT_SITE 132 132 Proton acceptor.
- Gene Ontology Go:
- cell cortex
membrane
plasma membrane
ATP binding
calcium ion binding
lipid binding
non-membrane spanning protein tyrosine kinase activity
protein serine/threonine kinase activity
apoptotic process
cell proliferation
G2/M transition of mitotic cell cycle
hemopoiesis
intracellular signal transduction
intrinsic apoptotic signaling pathway in response to oxidative stress
neural precursor cell proliferation
peptidyl-tyrosine phosphorylation
positive regulation of apoptotic process
protein autophosphorylation - Gene Ontology Biological Process:
- apoptotic process
cell proliferation
G2/M transition of mitotic cell cycle
hemopoiesis
intracellular signal transduction
intrinsic apoptotic signaling pathway in response to oxidative stress
neural precursor cell proliferation
peptidyl-tyrosine phosphorylation
positive regulation of apoptotic process
protein autophosphorylation - Gene Ontology Molecular Function:
- ATP binding
calcium ion binding
lipid binding
non-membrane spanning protein tyrosine kinase activity
protein serine/threonine kinase activity - Gene Ontology Cellular Component:
- cell cortex
membrane
plasma membrane - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Apoptosis
Calcium
Cell cycle
Cell membrane
Complete proteome
Kinase
Lipid-binding
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase - Interacts With:
- Q9BZR8