Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

MELK (Q14680) - Overview - Molecular Target Synopsis

Protein


MELK, Maternal embryonic leucine zipper kinase
Enzyme Classification 2.7.11.1
UniProt Q14680

Also Known as MELK_HUMAN, MELK, KIAA0175

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. Monomer. Interacts with ZNF622 and PPP1R8.

6GVX
CRYSTAL STRUCTURE OF MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE (MELK) IN COMPLEX WITH DORSOMORPHIN (COMPOUND C)
RCSB/PDB
Inspect Structure
See all 3D Structures for MELK

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MELK is active in the following subcellular-locations: cell membrane.
GO terms: MELK is active in the following subcellular-locations: cell cortex, cytoplasm, membrane, nucleus, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MELK has gain in 4 cell-lines, loss in 3 cell-lines and no signal in 996 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SF_268, SK_OV_3, BT_549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MKN-74, HUP-T3, PANC-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HMEC, NHLF, A549

(see details)

RNA Interference


MELK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: 93VU, MDAMB134VI. (see details)

3D Structures


For MELK there are:
30 structures (49 chains) solved
28 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

MELK is solved in complex with the approved drug(s):

XIN/NINTEDANIB (5MAF_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MELK has been screened with 1506 compounds (2224 bioactivities), 706 compounds have bioactivities that show binding affinity of <= 500nM (777 bioactivities). (see details)