InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Brsk1

Summary

InnateDB Protein

IDBP-138648.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Brsk1

Protein Name

BR serine/threonine kinase 1

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000039517

InnateDB Gene

IDBG-138646 (Brsk1)

Protein Structure

UniProt Annotation

Function

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-504' and 'Ser-554'. 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. {ECO:0000269PubMed:15705853, ECO:0000269PubMed:17482548, ECO:0000269PubMed:19648910, ECO:0000269PubMed:20026642}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Cell junction, synapse {ECO:0000250}. Note=Nuclear in the absence of DNA damage. Translocated to the nucleus in response to UV- or MMS-induced DNA damage. Localizes to synaptic vesicles in neurons (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Present in the gray matter of the brain and spinal cord (at protein level). Expressed in the nervous system, distributed within the brain and spinal cord of embryonic and postnatal animals. {ECO:0000269PubMed:15705853}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 3 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	3 [view]
Protein-Protein	3 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0043015	gamma-tubulin binding
GO:0050321	tau-protein kinase activity

Biological Process

GO:0006468	protein phosphorylation
GO:0006974	cellular response to DNA damage stimulus
GO:0007269	neurotransmitter secretion
GO:0007409	axonogenesis
GO:0009411	response to UV
GO:0030010	establishment of cell polarity
GO:0030182	neuron differentiation
GO:0031572	G2 DNA damage checkpoint
GO:0048812	neuron projection morphogenesis
GO:0051298	centrosome duplication

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005886	plasma membrane
GO:0008021	synaptic vesicle
GO:0030054	cell junction

Protein Structure and Domains

PDB ID

MGI:2685946

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR015940 Ubiquitin-associated/translation elongation factor EF1B, N-terminal, eukaryote
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00165
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt