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Gene Review

BRSK2  -  BR serine/threonine kinase 2

Homo sapiens

Synonyms: BR serine/threonine-protein kinase 2, Brain-selective kinase 2, Brain-specific serine/threonine-protein kinase 2, C11orf7, HUSSY-12, ...
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Disease relevance of BRSK2

  • No anti-BRSK2 antibodies were found in the serum of 50 patients with SCLC without PNS, 19 with limbic encephalitis without onconeural antibodies, 50 with anti-Hu antibodies and several paraneoplastic neurological syndromes, including 14 with limbic encephalitis, and 160 with a variety of non-paraneoplastic neurological syndromes [1].
  • We describe a new antigen, BR serine/threonine kinase 2 (BRSK2), identified by an antibody present in the serum of a patient with limbic encephalitis and small-cell lung cancer (SCLC) [1].
  • The present study examines the cellular defects in vivo and pathologic changes observed in SAD-1 mice at atmospheric oxygenation as well as the effect of acute hypoxia [2].

High impact information on BRSK2

  • A serine/threonine kinase SAD-1 in C. elegans regulates synapse development [3].
  • Adult SAD-1 transgenic mice were not anemic but had some abnormal features of erythrocytes and slightly enlarged spleens [4].
  • In earlier work, we showed that Sad1, the gene encoding the first committed enzyme in the avenacin pathway (beta-amyrin synthase), had arisen by duplication and divergence of a cycloartenol synthase-like gene [5].
  • We also demonstrate that two sodium azide-generated saponin-deficient mutants of oat, which define the Sad1 genetic complementation group, are defective in the gene encoding this enzyme and provide molecular genetic evidence indicating a direct link between AsbAS1, triterpenoid saponin biosynthesis, and disease resistance [6].
  • The predicted hsSAD1 protein comprises 778 amino acids and shares significant homology with the fission yeast Cdr2, a mitosis-regulatory kinase, and Caenorhabditis elegans SAD1, a neuronal cell polarity regulator [7].

Biological context of BRSK2

  • Furthermore, our study indicated that the kinase activity of BRSK2 can be increased through phosphorylation by PKA [8].
  • Less than 1% recombination was observed between Glu1 (on chromosome 10) and Sad1 [9].

Anatomical context of BRSK2

  • Eluted IgG from the BRSK2 clone gave a similar immunolabeling than the patient's serum by immunohistochemistry and immunoblot of rat brain and testis [1].
  • Probing a rat hippocampus expression library with the patient's serum resulted in the isolation of BR serine/threonine kinase 2 (BRSK2), a protein (also know as SAD1B kinase) preferentially expressed in the brain and testis and implicated in neuronal polarization as well as synaptic development [1].
  • In one of the five transgenic lines obtained, SAD-1, red blood cells contained 19% human Hb SAD (alpha 2 human 1 beta 2SAD) and mouse-human hybrids in addition to mouse hemoglobin [4].

Associations of BRSK2 with chemical compounds

  • BRSK2 is activated by cyclic AMP-dependent protein kinase A through phosphorylation at Thr260 [8].
  • Treatment with dithiothreitol reduced K(+)-Cl- cotransport activity in SAD-1 and beta-thal/SAD-1 mice to levels similar to that of control strains, indicating that reversible sulfhydryl oxidation contributes to the activated state of K(+)-Cl- cotransport in mouse erythrocytes that express transgenic human Hb SAD [10].

Enzymatic interactions of BRSK2

  • LKB1 can phosphorylate the Thr174 of BRSK2, increasing its activity >50-fold [8].

Other interactions of BRSK2


  1. BR serine/threonine kinase 2: a new autoantigen in paraneoplastic limbic encephalitis. Sabater, L., Gómez-Choco, M., Saiz, A., Graus, F. J. Neuroimmunol. (2005) [Pubmed]
  2. Sickle cell disease of transgenic SAD mice. Trudel, M., De Paepe, M.E., Chrétien, N., Saadane, N., Jacmain, J., Sorette, M., Hoang, T., Beuzard, Y. Blood (1994) [Pubmed]
  3. SAD: A Presynaptic Kinase Associated with Synaptic Vesicles and the Active Zone Cytomatrix that Regulates Neurotransmitter Release. Inoue, E., Mochida, S., Takagi, H., Higa, S., Deguchi-Tawarada, M., Takao-Rikitsu, E., Inoue, M., Yao, I., Takeuchi, K., Kitajima, I., Setou, M., Ohtsuka, T., Takai, Y. Neuron (2006) [Pubmed]
  4. Towards a transgenic mouse model of sickle cell disease: hemoglobin SAD. Trudel, M., Saadane, N., Garel, M.C., Bardakdjian-Michau, J., Blouquit, Y., Guerquin-Kern, J.L., Rouyer-Fessard, P., Vidaud, D., Pachnis, A., Roméo, P.H. EMBO J. (1991) [Pubmed]
  5. A different function for a member of an ancient and highly conserved cytochrome P450 family: From essential sterols to plant defense. Qi, X., Bakht, S., Qin, B., Leggett, M., Hemmings, A., Mellon, F., Eagles, J., Werck-Reichhart, D., Schaller, H., Lesot, A., Melton, R., Osbourn, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. A new class of oxidosqualene cyclases directs synthesis of antimicrobial phytoprotectants in monocots. Haralampidis, K., Bryan, G., Qi, X., Papadopoulou, K., Bakht, S., Melton, R., Osbourn, A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  7. Human SAD1 kinase is involved in UV-induced DNA damage checkpoint function. Lu, R., Niida, H., Nakanishi, M. J. Biol. Chem. (2004) [Pubmed]
  8. BRSK2 is activated by cyclic AMP-dependent protein kinase A through phosphorylation at Thr260. Guo, Z., Tang, W., Yuan, J., Chen, X., Wan, B., Gu, X., Luo, K., Wang, Y., Yu, L. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  9. New isozyme systems for maize (Zea mays L.): aconitate hydratase, adenylate kinase, NADH dehydrogenase, and shikimate dehydrogenase. Wendel, J.F., Goodman, M.M., Stuber, C.W., Beckett, J.B. Biochem. Genet. (1988) [Pubmed]
  10. Sulfhydryl oxidation and activation of red cell K(+)-Cl- cotransport in the transgenic SAD mouse. De Franceschi, L., Beuzard, Y., Brugnara, C. Am. J. Physiol. (1995) [Pubmed]
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