Q5RJI5

EV
Gene name
Brsk1 (Gm1100, Sadb)
Protein name
Serine/threonine-protein kinase BRSK1
Names
Brain-specific serine/threonine-protein kinase 1, BR serine/threonine-protein kinase 1, Serine/threonine-protein kinase SAD-B
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:381979
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)

592-603 (Autoinhibitory sequence, AIS) EV

Target domain

34-356 (KD-UBA domains)

Relief mechanism

Assay

Structural analysis, Split protein assay

Accessory elements

173-195 (Activation loop from InterPro)

Target domain

34-285 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

2 structures for Q5RJI5

Entry ID Method Resolution Chain Position Source
5IRI X-ray 280 A A/B 592-719 PDB
AF-Q5RJI5-F1 Predicted AlphaFoldDB

30 variants for Q5RJI5

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388871397 57 G>D No EVA
rs3388871446 130 P>L No EVA
rs3388837984 147 C>* No EVA
rs3388871436 206 K>Q No EVA
rs3397575330 260 S>R No EVA
rs3388881477 265 M>K No EVA
rs3388859073 266 I>N No EVA
rs3388859073 266 I>T No EVA
rs3388876580 288 G>E No EVA
rs3388876496 303 R>I No EVA
rs3388859080 315 L>Q No EVA
rs3388868278 331 D>V No EVA
rs3388874094 333 E>K No EVA
rs3388867414 336 H>Y No EVA
rs3388876597 386 M>I No EVA
rs3388875356 391 G>R No EVA
rs3388867408 397 R>L No EVA
rs3388876534 397 R>W No EVA
rs3388876553 432 S>N No EVA
rs3388871603 434 S>N No EVA
rs3388876463 555 S>T No EVA
rs3388875353 562 G>D No EVA
rs3388871462 598 N>I No EVA
rs3388868194 622 A>V No EVA
rs3388859034 647 E>* No EVA
rs3388859034 647 E>Q No EVA
rs3397197597 673 P>S No EVA
rs3397604704 674 E>G No EVA
rs3388868213 728 E>K No EVA
rs3397574515 748 P>A No EVA

No associated diseases with Q5RJI5

4 regional properties for Q5RJI5

Type Name Position InterPro Accession
domain Protein kinase domain 34 - 285 IPR000719
active_site Serine/threonine-protein kinase, active site 152 - 164 IPR008271
domain Ubiquitin-associated domain 314 - 356 IPR015940
binding_site Protein kinase, ATP binding site 40 - 63 IPR017441

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
  • Synapse
  • Presynaptic active zone
  • Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
  • Nuclear in the absence of DNA damage
  • Translocated to the nucleus in response to UV- or MMS-induced DNA damage (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
anchoring junction A cell junction that mechanically attaches a cell (and its cytoskeleton) to neighboring cells or to the extracellular matrix.
cell junction A cellular component that forms a specialized region of connection between two or more cells, or between a cell and the extracellular matrix, or between two membrane-bound components of a cell, such as flagella.
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.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
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.
presynaptic active zone A specialized region of the plasma membrane and cell cortex of a presynaptic neuron; encompasses a region of the plasma membrane where synaptic vesicles dock and fuse, and a specialized cortical cytoskeletal matrix.
synaptic vesicle A secretory organelle, typically 50 nm in diameter, of presynaptic nerve terminals; accumulates in high concentrations of neurotransmitters and secretes these into the synaptic cleft by fusion with the 'active zone' of the presynaptic plasma membrane.

8 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
gamma-tubulin binding Binding to the microtubule constituent protein gamma-tubulin.
magnesium ion binding Binding to a magnesium (Mg) ion.
molecular function inhibitor activity A molecular function regulator that inhibits or decreases the activity of its target via non-covalent binding that does not result in covalent modification to the target.
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.

20 GO annotations of biological process

Name Definition
associative learning Learning by associating a stimulus (the cause) with a particular outcome (the effect).
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.
cellular response to DNA damage stimulus 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.
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.
centrosome duplication The replication of a centrosome, a structure comprised of a pair of centrioles and peri-centriolar material from which a microtubule spindle apparatus is organized.
establishment of cell polarity The specification and formation of anisotropic intracellular organization or cell growth patterns.
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.
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.
neurotransmitter secretion The regulated release of neurotransmitter from the presynapse into the synaptic cleft via calcium-regulated exocytosis during synaptic transmission.
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 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).
regulation of synaptic plasticity A process that modulates synaptic plasticity, the ability of synapses to change as circumstances require. They may alter function, such as increasing or decreasing their sensitivity, or they may increase or decrease in actual numbers.
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.
synaptic vesicle cycle A biological process in which synaptic vesicles are loaded with neurotransmitters, move to the active zone, exocytose and are then recycled via endocytosis, ultimately leading to reloading with neurotransmitters.

17 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q8IWQ3 BRSK2 Serine/threonine-protein kinase BRSK2 Homo sapiens (Human) PR
Q8TDC3 BRSK1 Serine/threonine-protein kinase BRSK1 Homo sapiens (Human) SS
O35280 Chek1 Serine/threonine-protein kinase Chk1 Mus musculus (Mouse) PR
Q69Z98 Brsk2 Serine/threonine-protein kinase BRSK2 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
D3ZML2 Brsk2 Serine/threonine-protein kinase BRSK2 Rattus norvegicus (Rat) SS
B2DD29 Brsk1 Serine/threonine-protein kinase BRSK1 Rattus norvegicus (Rat) SS
Q19469 sad-1 Serine/threonine kinase SAD-1 Caenorhabditis elegans SS
10 20 30 40 50 60
MSSGSKEGGG GSPAYHLPHP HPHPPQHAQY VGPYRLEKTL GKGQTGLVKL GVHCITGQKV
70 80 90 100 110 120
AVKIVNREKL SESVLMKVER EIAILKLIEH PHVLKLHDVY ENKKYLYLVL EHVSGGELFD
130 140 150 160 170 180
YLVKKGRLTP KEARKFFRQI VSALDFCHSY SICHRDLKPE NLLLDEKNNI RIADFGMASL
190 200 210 220 230 240
QVGDSLLETS CGSPHYACPE VIKGEKYDGR RADMWSCGVI LFALLVGALP FDDDNLRQLL
250 260 270 280 290 300
EKVKRGVFHM PHFIPPDCQS LLRGMIEVEP EKRLSLEQIQ KHPWYLGGKH EPDPCLEPAP
310 320 330 340 350 360
GRRVAMRSLP SNGELDPDVL ESMASLGCFR DRERLHRELR SEEENQEKMI YYLLLDRKER
370 380 390 400 410 420
YPSCEDQDLP PRNDVDPPRK RVDSPMLSRH GKRRPERKSM EVLSITDAGS GGSPVPTRRA
430 440 450 460 470 480
LEMAQHSQRS RSVSGASTGL SSSPLSSPRS PVFSFSPEPG AGDEARGGGS PTSKTQTLPS
490 500 510 520 530 540
RGPRGGGAGE QPPPPSARST PLPGPPGSPR SSGGTPLHSP LHTPRASPTG TPGTTPPPSP
550 560 570 580 590 600
GGGVGGAAWR SRLNSIRNSF LGSPRFHRRK MQVPTAEEMS SLTPESSPEL AKRSWFGNFI
610 620 630 640 650 660
SLDKEEQIFL VLKDKPLSSI KADIVHAFLS IPSLSHSVLS QTSFRAEYKA SGGPSVFQKP
670 680 690 700 710 720
VRFQVDISSS EGPEPSPRRD GSSGGGIYSV TFTLISGPSR RFKRVVETIQ AQLLSTHDQP
730 740 750 760 770
SVQALADEKN GAQTRPAGTP PRSLQPPPGR SDPDLSSSPR RGPPKDKKLL ATNGTPLP