Q69Z98
Gene name |
Brsk2 (Kiaa4256, Sada) |
Protein name |
Serine/threonine-protein kinase BRSK2 |
Names |
Brain-specific serine/threonine-protein kinase 2, BR serine/threonine-protein kinase 2, Serine/threonine-protein kinase SAD-A |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:75770 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
SAD kinases, including SAD-A, are involved in neural development, cell cycle, and energy metabolism. They are part of the AMPK family and are essential for various biological processes. SAD-A contains a unique AIS that, along with the UBA domain, synergistically inhibits its kinase activity. This autoinhibition is crucial for the proper functioning of SAD kinases. AIS and UBA domain interact with the kinase domain to maintain SAD-A in an inactive state, which is important for its regulatory roles. The AIS plays a crucial role in its autoinhibition by interacting with the kinase domain (KD), orienting the αC helix into an inactive conformation and preventing the kinase from interacting with its substrates. The UBA domain of SAD-A also contributes to autoinhibition. It binds to the KD in a distinct mode, reinforcing the inactive conformation of the αC helix. The AIS, together with the KA1 domain, is necessary for phospholipid binding, suggesting a model where membrane association could trigger SAD kinase activation by relieving autoinhibition.
Autoinhibitory domains (AIDs)
Target domain |
531-636 (KA1 domain) |
Relief mechanism |
Ligand binding, Others |
Assay |
Structural analysis, Split protein assay, Mutagenesis experiment |
Target domain |
20-271 (Protein kinase domain) |
Relief mechanism |
Ligand binding, Others |
Assay |
Structural analysis, Split protein assay, Mutagenesis experiment |
Accessory elements
159-181 (Activation loop from InterPro)
Target domain |
20-271 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Autoinhibited structure
Activated structure
3 structures for Q69Z98
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 4YNZ | X-ray | 200 A | A/B | 15-342 | PDB |
| 4YOM | X-ray | 249 A | PDB | ||
| AF-Q69Z98-F1 | Predicted | AlphaFoldDB |
22 variants for Q69Z98
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388957048 | 32 | G>D | No | EVA | |
| rs3388918048 | 49 | K>N | No | EVA | |
| rs3388968480 | 151 | D>E | No | EVA | |
| rs3388962523 | 171 | S>N | No | EVA | |
| rs3398694290 | 178 | G>R | No | EVA | |
| rs3388956648 | 234 | F>Y | No | EVA | |
| rs3388960078 | 240 | I>F | No | EVA | |
| rs3388918032 | 243 | D>G | No | EVA | |
| rs224108357 | 258 | R>Q | No | EVA | |
| rs3388946032 | 268 | H>Y | No | EVA | |
| rs3388940645 | 274 | G>D | No | EVA | |
| rs3398749003 | 322 | D>A | No | EVA | |
| rs3398749010 | 325 | S>T | No | EVA | |
| rs3412803353 | 326 | E>* | No | EVA | |
| rs3398644637 | 347 | S>I | No | EVA | |
| rs3388934096 | 362 | P>S | No | EVA | |
| rs3388963275 | 386 | V>M | No | EVA | |
| rs3388956672 | 553 | H>L | No | EVA | |
| rs3388968412 | 562 | S>I | No | EVA | |
| rs3388956599 | 606 | N>I | No | EVA | |
| rs3388945976 | 643 | A>V | No | EVA | |
| rs3388964809 | 660 | L>F | No | EVA |
No associated diseases with Q69Z98
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
5 GO annotations of cellular component
| Name | Definition |
|---|---|
| centrosome | A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| distal axon | That part of an axon close to and including the growth cone or the axon terminus. |
| endoplasmic reticulum | The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). |
| perinuclear region of cytoplasm | Cytoplasm situated near, or occurring around, the nucleus. |
7 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| ATPase binding | Binding to an ATPase, any enzyme that catalyzes the hydrolysis of ATP. |
| magnesium ion binding | Binding to a magnesium (Mg) ion. |
| protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
| protein serine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. |
| protein serine/threonine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. |
| tau-protein kinase activity | Catalysis of the reaction: ATP + tau-protein = ADP + O-phospho-tau-protein. |
18 GO annotations of biological process
| Name | Definition |
|---|---|
| actin cytoskeleton reorganization | A process that is carried out at the cellular level which results in dynamic structural changes to the arrangement of constituent parts of cytoskeletal structures comprising actin filaments and their associated proteins. |
| axonogenesis | De novo generation of a long process of a neuron, including the terminal branched region. Refers to the morphogenesis or creation of shape or form of the developing axon, which carries efferent (outgoing) action potentials from the cell body towards target cells. |
| cell division | The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells. |
| cellular response to glucose starvation | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of glucose. |
| ERAD pathway | The protein catabolic pathway which targets endoplasmic reticulum (ER)-resident proteins for degradation by the cytoplasmic proteasome. It begins with recognition of the ER-resident protein, includes retrotranslocation (dislocation) of the protein from the ER to the cytosol, protein modifications necessary for correct substrate transfer (e.g. ubiquitination), transport of the protein to the proteasome, and ends with degradation of the protein by the cytoplasmic proteasome. |
| establishment of cell polarity | The specification and formation of anisotropic intracellular organization or cell growth patterns. |
| exocytosis | A process of secretion by a cell that results in the release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle. Exocytosis can occur either by full fusion, when the vesicle collapses into the plasma membrane, or by a kiss-and-run mechanism that involves the formation of a transient contact, a pore, between a granule (for exemple of chromaffin cells) and the plasma membrane. The latter process most of the time leads to only partial secretion of the granule content. Exocytosis begins with steps that prepare vesicles for fusion with the membrane (tethering and docking) and ends when molecules are secreted from the cell. |
| G2/M transition of mitotic cell cycle | The mitotic cell cycle transition by which a cell in G2 commits to M phase. The process begins when the kinase activity of M cyclin/CDK complex reaches a threshold high enough for the cell cycle to proceed. This is accomplished by activating a positive feedback loop that results in the accumulation of unphosphorylated and active M cyclin/CDK complex. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to a stimulus indicating endoplasmic reticulum (ER) stress, and ends when the execution phase of apoptosis is triggered. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen. |
| microtubule cytoskeleton organization involved in establishment of planar polarity | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising microtubules and their associated proteins and contributes to the establishment of planar polarity. |
| neuron differentiation | The process in which a relatively unspecialized cell acquires specialized features of a neuron. |
| neuron projection morphogenesis | The process in which the anatomical structures of a neuron projection are generated and organized. A neuron projection is any process extending from a neural cell, such as axons or dendrites. |
| peptidyl-serine phosphorylation | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of axonogenesis | Any process that modulates the frequency, rate or extent of axonogenesis, the generation of an axon, the long process of a neuron. |
| regulation of insulin secretion involved in cellular response to glucose stimulus | Any process that modulates the frequency, rate or extent of the regulated release of insulin that contributes to the response of a cell to glucose. |
| regulation of neuron projection development | Any process that modulates the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites). |
17 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q8TDC3 | BRSK1 | Serine/threonine-protein kinase BRSK1 | Homo sapiens (Human) | SS |
| Q8IWQ3 | BRSK2 | Serine/threonine-protein kinase BRSK2 | Homo sapiens (Human) | PR |
| O35280 | Chek1 | Serine/threonine-protein kinase Chk1 | Mus musculus (Mouse) | PR |
| Q5RJI5 | Brsk1 | Serine/threonine-protein kinase BRSK1 | Mus musculus (Mouse) | EV |
| Q61846 | Melk | Maternal embryonic leucine zipper kinase | Mus musculus (Mouse) | PR |
| O54863 | Tssk2 | Testis-specific serine/threonine-protein kinase 2 | Mus musculus (Mouse) | PR |
| Q61241 | Tssk1b | Testis-specific serine/threonine-protein kinase 1 | Mus musculus (Mouse) | PR |
| Q8C0X8 | Sperm motility kinase X | Mus musculus (Mouse) | PR | |
| A0AUV4 | Gm7168 | Sperm motility kinase Y | Mus musculus (Mouse) | PR |
| Q8C0N0 | Gm4922 | Sperm motility kinase Z | Mus musculus (Mouse) | PR |
| Q641K5 | Nuak1 | NUAK family SNF1-like kinase 1 | Mus musculus (Mouse) | PR |
| Q5EG47 | Prkaa1 | 5'-AMP-activated protein kinase catalytic subunit alpha-1 | Mus musculus (Mouse) | SS |
| Q8BRK8 | Prkaa2 | 5'-AMP-activated protein kinase catalytic subunit alpha-2 | Mus musculus (Mouse) | SS |
| A2KF29 | Smoktcr | Sperm motility kinase Tcr mutant form | Mus musculus (Mouse) | PR |
| B2DD29 | Brsk1 | Serine/threonine-protein kinase BRSK1 | Rattus norvegicus (Rat) | SS |
| D3ZML2 | Brsk2 | Serine/threonine-protein kinase BRSK2 | Rattus norvegicus (Rat) | SS |
| Q19469 | sad-1 | Serine/threonine kinase SAD-1 | Caenorhabditis elegans | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MTSTGKDGGG | AQHAQYVGPY | RLEKTLGKGQ | TGLVKLGIHC | VTCQKVAIKI | VNREKLSESV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| LMKVEREIAI | LKLIEHPHVL | KLHDVYENKK | YLYLVLEHVS | GGELFDYLVK | KGRLTPKEAR |
| 130 | 140 | 150 | 160 | 170 | 180 |
| KFFRQIISAL | DFCHSHSICH | RDLKPENLLL | DERNNIRIAD | FGMASLQVGD | SLLETSCGSP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| HYACPEVIRG | EKYDGRKADV | WSCGVILFAL | LVGALPFDDD | NLRQLLEKVK | RGVFHMPHFI |
| 250 | 260 | 270 | 280 | 290 | 300 |
| PPDCQSLLRG | MIEVDAARRL | TLEHIQKHIW | YIGGKNEPEP | EQPIPRKVQI | RSLPSLEDID |
| 310 | 320 | 330 | 340 | 350 | 360 |
| PDVLDSMHSL | GCFRDRNKLL | QDLLSEEENQ | EKMIYFLLLD | RKERYPSHED | EDLPPRNEID |
| 370 | 380 | 390 | 400 | 410 | 420 |
| PPRKRVDSPM | LNRHGKRRPE | RKSMEVLSVT | DGGSPVPARR | AIEMAQHGQR | SRSISGASSG |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LSTSPLSSPR | VTPHPSPRGS | PLPTPKGTPV | HTPKESPAGT | PNPTPPSSPS | VGGVPWRTRL |
| 490 | 500 | 510 | 520 | 530 | 540 |
| NSIKNSFLGS | PRFHRRKLQV | PTPEEMSNLT | PESSPELAKK | SWFGNFINLE | KEEQIFVVIK |
| 550 | 560 | 570 | 580 | 590 | 600 |
| DKPLSSIKAD | IVHAFLSIPS | LSHSVISQTS | FRAEYKATGG | PAVFQKPVKF | QVDITYTEGG |
| 610 | 620 | 630 | 640 | 650 | 660 |
| EAQKENGIYS | VTFTLLSGPS | RRFKRVVETI | QAQLLSTHDQ | PSAQHLSDTT | NCMEVMTGRL |
| 670 | 680 | 690 | 700 | 710 | 720 |
| SKCGTPLSNF | FDVIKQLFSD | EKNGQAAQAP | STPAKRSAHG | PLGDSAAAGP | GGDTEYPMGK |
| 730 | |||||
| DMAKMGPPAA | RREQP |