D3ZML2

SS
Gene name
Brsk2 (Sada)
Protein name
Serine/threonine-protein kinase BRSK2
Names
EC 2.7.11.1 , EC 2.7.11.26 , Brain-specific serine/threonine-protein kinase 2 , BR serine/threonine-protein kinase 2 , Serine/threonine-protein kinase SAD-A
Species
Rattus norvegicus (Rat)
KEGG Pathway
EC number
2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

SAD-B is a serine/threonine kinase involved in neuronal development, cell cycle, and energy metabolism. It is highly expressed in the brain and plays a role in axonal arborization, nerve terminal maturation, and neurotransmitter release. SAD-B contains an AIS near the KA1 domain that regulates its activity. This sequence is flexible and solvent-accessible, allowing it to interact with the kinase domain (KD) and ubiquitin-associated (UBA) domain to inhibit SAD-B activity. The crystal structure of the mouse SAD-B AIS-KA1 fragment reveals that the AIS is highly flexible in its isolated state, suggesting its readiness to bind to the KD-UBA junction for autoinhibition. Furthermore, the biochemical experiments demonstrate that the AIS of SAD-B non-competitively inhibits the kinase activity of SAD-B, similar to the autoinhibition observed in SAD-A, indicating a conserved mechanism between these kinases.

Autoinhibitory domains (AIDs)

519-530 (Autoinhibitory sequence, AIS) SS

Target domain

20-340 (KD-UBA domains)

Relief mechanism

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

0 structures for D3ZML2

Entry ID Method Resolution Chain Position Source
No available structures

No variants for D3ZML2

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for D3ZML2

No associated diseases with D3ZML2

4 regional properties for D3ZML2

Type Name Position InterPro Accession
domain Protein kinase domain 20 - 271 IPR000719
active_site Serine/threonine-protein kinase, active site 138 - 150 IPR008271
binding_site Protein kinase, ATP binding site 26 - 49 IPR017441
domain BRSK1/2-like, UBA domain 298 - 351 IPR048622

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
  • Cytoplasm, perinuclear region
  • Endoplasmic reticulum
  • Detected at centrosomes during mitosis
  • Localizes to the endoplasmic reticulum in response to stress caused by tunicamycin (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 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).
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
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
protein serine/threonine kinase activity Catalysis of the reactions
tau-protein kinase activity Catalysis of the reaction

18 GO annotations of biological process

Name Definition
actin cytoskeleton organization 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 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.
DNA damage response 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 a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
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.
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.
mitotic G2 DNA damage checkpoint signaling A mitotic cell cycle checkpoint that detects and negatively regulates progression through the G2/M transition of the cell cycle in response to DNA damage.
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.
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).
response to UV Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ultraviolet radiation (UV light) stimulus. Ultraviolet radiation is electromagnetic radiation with a wavelength in the range of 10 to 380 nanometers.

12 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
Q5RJI5 Brsk1 Serine/threonine-protein kinase BRSK1 Mus musculus (Mouse) EV
Q69Z98 Brsk2 Serine/threonine-protein kinase BRSK2 Mus musculus (Mouse) EV
B2DD29 Brsk1 Serine/threonine-protein kinase BRSK1 Rattus norvegicus (Rat) SS
Q91ZN7 Chek1 Serine/threonine-protein kinase Chk1 Rattus norvegicus (Rat) PR
P54645 Prkaa1 5'-AMP-activated protein kinase catalytic subunit alpha-1 Rattus norvegicus (Rat) EV
Q09137 Prkaa2 5'-AMP-activated protein kinase catalytic subunit alpha-2 Rattus norvegicus (Rat) EV
Q6ZLP5 CIPK23 CBL-interacting protein kinase 23 Oryza sativa subsp japonica (Rice) PR
Q5JLQ9 CIPK30 CBL-interacting protein kinase 30 Oryza sativa subsp japonica (Rice) PR
Q6ERS4 CIPK16 CBL-interacting protein kinase 16 Oryza sativa subsp japonica (Rice) PR
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 PESSPELGHL QLFGNPVSKV RSVAMELVIL
550 560 570 580 590 600
VQTLAYTSFR LLGTFLPVRY LRHSVLSRPP ERARLVLRGA PCTHMGPVWN MVGMAYTQNP
610 620 630 640 650 660
PIMGETGVYG SQWVMSSAPS KHYTSLGLSV PSPSCSLSPS LFPFCAPDTT NCMEVMTGRL
670 680 690 700 710 720
SKCGTPLSNF FDVIKQLFSD EKNGQAAQAP STPAKRSAHG PLGDSAAAGP GGDTEYPMGK
730
DMAKMGPPAA RREQP