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

BRSK1 (Q8TDC3) - Overview - Molecular Target Synopsis

Protein


BRSK1, Serine/threonine-protein kinase BRSK1
Enzyme Classification 2.7.11.1
UniProt Q8TDC3

Also Known as BRSK1_HUMAN, BRSK1, KIAA1811, SAD1, SADB

Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in post-mitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: BRSK1 is active in the following subcellular-locations: cell junction, centrosome, cytoplasm, cytoskeleton, microtubule organizing center, nucleus, synapse.
GO terms: BRSK1 is active in the following subcellular-locations: cell junction, centrosome, cytoplasm, distal axon, nucleoplasm, nucleus, presynaptic active zone, synaptic vesicle.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project BRSK1 has gain in 2 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are:

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC12, SK-N-FI, NCI-H1155

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, K562, IMR-90

(see details)

RNA Interference


BRSK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SKOV3, SIHA. (see details)

3D Structures


At greater than 90% identity similarity to BRSK1 there are:
1 structures (2 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


BRSK1 has been screened with 702 compounds (1294 bioactivities), 5 compounds have bioactivities that show binding affinity of <= 500nM (7 bioactivities). (see details)