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

MARK2 (Q7KZI7) - Overview - Molecular Target Synopsis

Protein


MARK2, Serine/threonine-protein kinase MARK2
Enzyme Classification 2.7.11.1
UniProt Q7KZI7

Also Known as MARK2_HUMAN, MARK2, EMK1

Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. Homodimer. Interacts with PAK5; leading to inhibit the protein kinase activity (By similarity). Interacts with MAPT/TAU (PubMed:23666762). Interacts with MTCL1 isoform 1; the interaction is direct and increases MARK2 microtubule-binding ability (PubMed:23902687). Interacts (when phosphorylated at Thr-596) with YWHAZ (PubMed:15324659).

5KZ8
MARK2 COMPLEX WITH 7-[(1S)-1-(4-FLUOROPHENYL)ETHYL]-5,5-DIMETHYL-2-(3- PYRIDYLAMINO)PYRROLO[2,3-D]PYRIMIDIN-6-ONE
RCSB/PDB
Inspect Structure
See all 3D Structures for MARK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MARK2 is active in the following subcellular-locations: cell membrane, cell projection, cytoplasm, cytoskeleton, dendrite, lateral cell membrane.
GO terms: MARK2 is active in the following subcellular-locations: actin filament, cytoplasm, dendrite, lateral plasma membrane, membrane, microtubule bundle, mitochondrion, nucleoplasm, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MARK2 has gain in 3 cell-lines, loss in 0 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: CCRF_CEM, HCC_2998, HL_60

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: CAL 27, HT-29, NCI-H727

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, A549, HeLa-S3

(see details)

RNA Interference


MARK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MIAPACA2, OE19. (see details)

3D Structures


For MARK2 there are:
5 structures (12 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MARK2 has been screened with 773 compounds (1390 bioactivities), 9 compounds have bioactivities that show binding affinity of <= 500nM (18 bioactivities). (see details)