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

MARK4 (Q96L34) - Overview - Molecular Target Synopsis

Protein


MARK4, MAP/microtubule affinity-regulating kinase 4
Enzyme Classification 2.7.11.1
UniProt Q96L34

Also Known as MARK4_HUMAN, MARK4, KIAA1860, MARKL1

Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942). Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:14594945, PubMed:23666762). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532). Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal cell survival (PubMed:15009667). Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942). Interacts with MAPT/TAU (PubMed:23666762). Interacts with gamma-tubulin (PubMed:14594945). Interacts with ODF2 (PubMed:23400999). Interacts with USP9X (PubMed:18254724).

5ES1
CRYSTAL STRUCTURE OF MICROTUBULE AFFINITY-REGULATING KINASE 4 CATALYTIC DOMAIN IN COMPLEX WITH A PYRAZOLOPYRIMIDINE INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for MARK4

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MARK4 is active in the following subcellular-locations: cell projection, centrosome, cilium axoneme, cilium basal body, cytoplasm, cytoskeleton, dendrite, microtubule organizing center.
GO terms: MARK4 is active in the following subcellular-locations: centrosome, ciliary basal body, cytoplasm, cytosol, dendrite, gamma-tubulin complex, microtubule cytoskeleton, microtubule organizing center, midbody, neuron projection.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MARK4 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: HOP_62, CCRF_CEM, SF_539

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H820, HOP-62, OVCAR433

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: SK-N-SH, HeLa-S3, BJ

(see details)

RNA Interference


MARK4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM44, DU4475. (see details)

3D Structures


For MARK4 there are:
1 structures (1 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MARK4 has been screened with 537 compounds (954 bioactivities), 6 compounds have bioactivities that show binding affinity of <= 500nM (10 bioactivities). (see details)