Serine/threonine-protein kinase BRSK1 (BRSK1)

The protein contains 778 amino acids for an estimated molecular weight of 85087 Da.

 

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 postmitotic 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. (updated: Oct. 16, 2019)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 50%
Model score: 0
No model available.

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VariantDescription
a gastric adenocarcinoma sample
a lung large cell carcinoma sample; somatic mutation
a metastatic melanoma sample; somatic mutation
dbSNP:rs55892637
dbSNP:rs12978445
dbSNP:rs55796422

The reference OMIM entry for this protein is 609235

Br serine/threonine kinase 1; brsk1
Kiaa1811

CLONING

By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (2001) cloned BRSK1, which they designated KIAA1811. The deduced 715-amino acid protein shares 75% identity with BRSK2 (609236). The first methionine was not found within a Kozak context, indicating the cDNA may be incomplete. RT-PCR ELISA detected highest expression in adult brain, followed by fetal brain and adult spinal cord. Intermediate expression was detected in adult heart, pancreas, testis, ovary, lung, and kidney, and in fetal liver. Adult liver, spleen, and skeletal muscle showed little to no expression. All specific adult brain regions examined showed intermediate to high BRSK1 expression, with highest levels in caudate nucleus and substantia nigra.

MAPPING

By genomic sequence analysis, Nagase et al. (2001) mapped the BRSK1 gene to chromosome 19.

MOLECULAR GENETICS

For discussion of an association between variation in the BRSK1 gene and age at natural menopause, see MENOQ2 (612884).

ANIMAL MODEL

Kishi et al. (2005) showed that SAD-A (BRSK2) and SAD-B (BRSK1), mammalian orthologs of a kinase needed for presynaptic differentiation in Caenorhabditis elegans, are required for neuronal polarization. Kishi et al. (2005) generated mice null for both SAD-A and SAD-B. Mice homozygous for deletion of only 1 gene were healthy and fertile, but double-knockout pups showed little spontaneous movement, were only weakly responsive to tactile stimulation, and died within 2 hours of birth. At embryonic day 19, principal divisions of brain, spinal cord, and peripheral nervous system had formed, but the forebrain was noticeably smaller in double-mutant embryos than in littermate controls. Double-mutant neurons often had a starburst morphology or processes that ran diagonally or tangentially rather than radially and axons were difficult to distinguish from dendrites. ... More on the omim web site

Subscribe to this protein entry history

Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 609235 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).