serine/threonine protein kinase BRSK1; brain-specific serine/threonine protein kinase 1; BR serine/threonine protein kinase 1; serine/threonine protein kinase SAD-B; synapses of amphids defective homolog 1; SAD1 homolog; hSAD1 (BRSK1, KIAA1811, SAD1, SADB)

Function: - serine/threonine protein kinase - role in polarization of neurons & centrosome duplication - phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 & WEE1 - following phosphorylation & 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 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 & plays a role in neurotransmitter release, possibly by phosphorylating RIMS1 - acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 & TUBG2) at Ser-131, leading to translocation of gamma-tubulin & its associated proteins to the centrosome - role in UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation & activation of WEE1, & inhibition of CDC25B & CDC25C - comment: would seem to both activate & inactivate WEE1 - activated by phosphorylation on Thr-189 by STK11/LKB1 - phosphorylated at Thr-189 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase & CAB39 - not phosphorylated at Thr-189 by CaMKK2 - in contrast, it is phosphorylated & activated by CaMKK - may be inactivated via dephosphorylation of Thr-189 by PP2C Cofactor: Mg⁺² (putative) Structure: - belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family, SNF1 subfamily - contains 1 protein kinase domain - contains 1 UBA domain Compartment: - cytoplasm, nucleus - cytoskeleton, centrosome (putative) - cell junction, synapse - localizes to synaptic vesicles in neurons - cytoplasmic in the absence of DNA damage - translocated to the nucleus in response to UV- or MMS- induced DNA damage Alternative splicing: named isoforms=3 Expression: - widely expressed - highest levels in brain & testis - protein levels remain constant throughout the cell cycle

Properties

SIZE: entity length = 778 aa MW = 85 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: kinase domain SITE: 34-285 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 40-48 ATP-binding site NAME: ATP-binding site SITE: 63-63 aspartate residue {D156} Thr phosphorylation site {T189} Ser phosphorylation site {S193} UBA domain {314-356} Ser phosphorylation site {S447} proline-rich region SITE: 492-540 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S508} Ser phosphorylation site {S563}

Database Correlations

OMIM 609235 UniProt Q8TDC3 Pfam PF00069 Entrez Gene 84446 Kegg hsa:84446 ENZYME correlations

References

UniProt :accession Q8TDC3