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

TAOK2 (Q9UL54) - Overview - Molecular Target Synopsis

Protein


TAOK2, Serine/threonine-protein kinase TAO2
Enzyme Classification 2.7.11.1
UniProt Q9UL54

Also Known as TAOK2_HUMAN, TAOK2, KIAA0881, MAP3K17, PSK, PSK1

Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. Interacts with MAP2K3 and MAP2K6 (By similarity). Self-associates. Interacts with tubulins through the C-terminal domain. Interacts with MAP3K7 and interfers with MAP3K7-binding to CHUK and thus prevents NF-kappa-B activation. Isoform 2 interacts with PCDH8; this complex may also include CDH2.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: TAOK2 is active in the following subcellular-locations: cell projection, cytoplasm, cytoplasmic vesicle membrane, cytoskeleton, dendrite, nucleus.
GO terms: TAOK2 is active in the following subcellular-locations: actin cytoskeleton, axon, axonal growth cone, cytoplasm, cytoplasmic vesicle, cytoplasmic vesicle membrane, cytosol, dendritic growth cone, integral component of membrane, neuron projection, nucleolus, nucleus, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TAOK2 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_28, HCT_15, NCI_H322M

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H1155, SNU-398, G111

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, HUVEC, K562

(see details)

RNA Interference


TAOK2 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, CROE33. (see details)

3D Structures


At greater than 90% identity similarity to TAOK2 there are:
3 structures (6 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TAOK2 has been screened with 293 compounds (464 bioactivities), 10 compounds have bioactivities that show binding affinity of <= 500nM (10 bioactivities). (see details)