D3ZML2 (BRSK2_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 36. History...
Names and origin
|Protein names||Recommended name:|
Serine/threonine-protein kinase BRSK2
Brain-specific serine/threonine-protein kinase 2
Short name=BR serine/threonine-protein kinase 2
Serine/threonine-protein kinase SAD-A
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||735 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 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-523' and 'Ser-573'. 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. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-175 can inhibit insulin secretion, BRSK2 phosphorylated at Thr-261 can promote insulin secretion. Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmatic reticulum (ER) stress By similarity.
ATP + a protein = ADP + a phosphoprotein.
ATP + [tau protein] = ADP + [tau protein] phosphate.
Magnesium By similarity.
Activated by phosphorylation on Thr-175 by STK11/LKB1 By similarity.
Interacts with FZR1, a regulatory subunit of the APC ubiquitin ligase complex. Interacts with COPS5. Interacts with PAK1 By similarity.
Cytoplasm › cytoskeleton › microtubule organizing center › centrosome By similarity. Cytoplasm › perinuclear region By similarity. Endoplasmic reticulum By similarity. Note: Detected at centrosomes during mitosis. Localizes to the endoplasmic reticulum in response to stress caused by tunicamycin By similarity.
May be phosphorylated at Thr-261 by PKA By similarity. Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-175 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-175 by PP2C By similarity.
Polyubiquitinated by the APC complex in conjunction with FZR1, leading to its proteasomal degradation. Targeted for proteasomal degradation by interaction with COPS5. BRSK2 levels change during the cell cycle. BRSK2 levels are low at the G1/S boundary and gradually increase as cells progress into G2 phase. BRSK2 levels decrease rapidly at the end of mitosis By similarity.
Protein synthesis is inhibited by the TSC1-TSC2 complex acting through TORC1 in neurons, leading to regulate neuron polarization (Ref.3).
Contains 1 protein kinase domain.
Contains 1 UBA domain.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: D3ZML2-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform 2 (identifier: D3ZML2-2) |
The sequence of this isoform differs from the canonical sequence as follows:
409-409: Q → QSKAVFSKSLDIAEAHPQFSKED
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 735||735||Serine/threonine-protein kinase BRSK2||PRO_0000412650|
|Domain||20 – 271||252||Protein kinase|
|Domain||298 – 340||43||UBA|
|Nucleotide binding||26 – 34||9||ATP By similarity|
|Compositional bias||425 – 469||45||Pro-rich|
|Active site||142||1||Proton acceptor By similarity|
|Binding site||49||1||ATP By similarity|
Amino acid modifications
|Modified residue||175||1||Phosphothreonine; by LKB1 By similarity|
|Modified residue||261||1||Phosphothreonine; by PKA By similarity|
|Modified residue||368||1||Phosphoserine By similarity|
|Modified residue||383||1||Phosphoserine By similarity|
|Modified residue||394||1||Phosphoserine By similarity|
|Modified residue||413||1||Phosphoserine By similarity|
|Modified residue||423||1||Phosphothreonine By similarity|
|Modified residue||510||1||Phosphothreonine By similarity|
|Alternative sequence||409||1||Q → QSKAVFSKSLDIAEAHPQFS KED in isoform 2.||VSP_041747|
|Sequence conflict||383||1||S → C in CAJ13860. Ref.2|
|||"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."|
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
|||"BR serine/threonine Kinase 2: a new autoantigen in paraneoplastic limbic encephalitis."|
Sabater L., Gomez-Choco M., Saiz A., Graus F.
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-457 (ISOFORM 2).
|||"Tuberous sclerosis complex proteins control axon formation."|
Choi Y.J., Di Nardo A., Kramvis I., Meikle L., Kwiatkowski D.J., Sahin M., He X.
Genes Dev. 22:2485-2495(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION OF TRANSLATION.
|AM040976 mRNA. Translation: CAJ13860.1.|
3D structure databases
Protein-protein interaction databases
Protocols and materials databases
|RGD||1566256. Brsk2. |
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 1 hit. |
|SMART||SM00220. S_TKc. 1 hit. |
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. False negative.
|Accession||Primary (citable) accession number: D3ZML2|
Secondary accession number(s): E9PTC7, Q4A1P4
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families