P18431

SS
Gene name
sgg (gsk3, zw3, CG2621)
Protein name
Protein kinase shaggy
Names
EC 2.7.11.1 , Protein zeste-white 3
Species
Drosophila melanogaster (Fruit fly)
KEGG Pathway
dme:Dmel_CG2621
EC number
2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

Glycogen synthase kinase 3-beta (GSK3B) is a Ser/Thr protein kinase with key roles in transduction of regulatory and proliferative signals. When the N-terminal peptide is phosphorylated (Ser 9), it autoinhibits GSK-3 by acting as a pseudo-substrate that blocks binding of other substrates. Unique to GSK-3, the binding is associated with a drastic conformational rearrangement of a highly conserved loop that engages the inhibitory peptides in a clamp-like structure. And it shows dose-dependent inhibition of GSK3B kinase activity. In addition, the deletion of the N-terminal residues increased GSK3B catalytic activity by two folds.

Autoinhibitory domains (AIDs)

3-12 (N-terminal autoinhibitory segment) SS

Target domain

54-338 (Protein kinase domain)

Relief mechanism

PTM

Assay

Accessory elements

197-219 (Activation loop from InterPro)

Target domain

50-341 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for P18431

Entry ID Method Resolution Chain Position Source
AF-P18431-F1 Predicted AlphaFoldDB

No variants for P18431

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P18431

No associated diseases with P18431

4 regional properties for P18431

Type Name Position InterPro Accession
domain Protein kinase domain 54 - 338 IPR000719
active_site Serine/threonine-protein kinase, active site 175 - 187 IPR008271
binding_site Protein kinase, ATP binding site 60 - 84 IPR017441
domain Glycogen synthase kinase 3, catalytic domain 50 - 341 IPR039192

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
  • Cytoplasm, cell cortex
  • Synapse
  • Cell projection, axon
  • In syncytial embryos, detected at the centrosomes throughout the cell cycle, and in the mitotic spindle and pseudocleavage furrows invaginating from the cell cortex during mitosis
  • Concentrated at the growing end of membranes during the cellularization process
  • After cellularization, localized to the centrosomes during mitosis and to the nucleus at the end of telophase
  • Enriched in the presynaptic side of the neuromuscular junction, with some signal detected also in axonal branches
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

13 GO annotations of cellular component

Name Definition
axon The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter.
beta-catenin destruction complex A cytoplasmic protein complex containing glycogen synthase kinase-3-beta (GSK-3-beta), the adenomatous polyposis coli protein (APC), and the scaffolding protein axin, among others; phosphorylates beta-catenin, targets it for degradation by the proteasome.
cell cortex The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
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.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
female germline ring canal An intercellular bridge that connects the germline cells of a female cyst.
fusome A large intracellular spectrin-rich structure that has been found in insect germline cells and mammalian hematopoietic cells. The fusome is an elongated, branched structure, formed from the spherical spectrosome organelle.
mitotic spindle A spindle that forms as part of mitosis. Mitotic and meiotic spindles contain distinctive complements of proteins associated with microtubules.
neuromuscular junction The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
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.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

4 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
protein serine kinase activity Catalysis of the reactions
protein serine/threonine kinase activity Catalysis of the reactions
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions

43 GO annotations of biological process

Name Definition
cell differentiation The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
chaeta development The process whose specific outcome is the progression of a chaeta over time, from its formation to the mature structure. A chaeta is a sensory multicellular cuticular outgrowth of a specifically differentiated cell.
chaeta morphogenesis The process in which the anatomical structures of the chaeta are generated and organized. A chaeta is a sensory multicellular cuticular outgrowth of a specifically differentiated cell.
chitin-based larval cuticle pattern formation The process that gives rise to the patterns of cell differentiation in the chitin-based larval cuticle. An example of this is found in Drosophila melanogaster.
circadian rhythm Any biological process in an organism that recurs with a regularity of approximately 24 hours.
entrainment of circadian clock The synchronization of a circadian rhythm to environmental time cues such as light.
epithelial cell morphogenesis The change in form that occurs when an epithelial cell progresses from its initial formation to its mature state.
establishment of epithelial cell planar polarity The specification and formation of the polarity of an epithelial cell along the plane of the epithelial tissue.
extrinsic apoptotic signaling pathway in absence of ligand The series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with withdrawal of a ligand from a cell surface receptor, and ends when the execution phase of apoptosis is triggered.
female meiotic nuclear division A cell cycle process by which the cell nucleus divides as part of a meiotic cell cycle in the female germline.
follicle cell of egg chamber development The process that occurs during oogenesis involving the ovarian follicle cells, somatic cells which surround the germ cells of an ovary. An example of this is found in Drosophila melanogaster.
glycogen metabolic process The chemical reactions and pathways involving glycogen, a polydisperse, highly branched glucan composed of chains of D-glucose residues in alpha-(1->4) glycosidic linkage, joined together by alpha-(1->6) glycosidic linkages.
habituation A decrease in a behavioral response to a repeated stimulus. This is exemplified by the failure of a person to show a startle response to a loud noise that has been repeatedly presented.
heart development The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
imaginal disc-derived wing margin morphogenesis The process in which the anatomical structures of the imaginal disc-derived wing margin are generated and organized. The wing margin is a strip of cells in the third instar disc at the boundary between the presumptive dorsal and ventral surfaces of the wing blade.
insulin receptor signaling pathway The series of molecular signals generated as a consequence of the insulin receptor binding to insulin.
locomotor rhythm The rhythm of the locomotor activity of an organism during its 24 hour activity cycle.
negative regulation of canonical Wnt signaling pathway Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes.
negative regulation of insulin receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of insulin receptor signaling.
negative regulation of smoothened signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of smoothened signaling.
negative regulation of synaptic assembly at neuromuscular junction Any process that stops, prevents, or reduces the frequency, rate or extent of synaptic assembly at neuromuscular junction.
olfactory learning Any process in an organism in which a relatively long-lasting adaptive behavioral change occurs in response to (repeated) exposure to an olfactory cue.
oogenesis The complete process of formation and maturation of an ovum or female gamete from a primordial female germ cell. Examples of this process are found in Mus musculus and Drosophila melanogaster.
phosphorylation The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
positive regulation of mitotic metaphase/anaphase transition Any process that activates or increases the frequency, rate or extent of the cell cycle process in which a cell progresses from metaphase to anaphase during mitosis, triggered by the activation of the anaphase promoting complex by Cdc20/Sleepy homolog which results in the degradation of Securin.
positive regulation of proteasomal ubiquitin-dependent protein catabolic process Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
positive regulation of proteolysis involved in protein catabolic process Any process that activates or increases the frequency, rate or extent of proteolysis involved in protein catabolic process.
positive regulation of ubiquitin-dependent protein catabolic process Any process that activates or increases the frequency, rate or extent of ubiquitin-dependent protein catabolic process.
pseudocleavage involved in syncytial blastoderm formation Formation of furrows in the cytoplasm between nuclei during cell cycles in embryos that contribute to the formation of the syncytial blastoderm. An example of this process is found in Drosophila melanogaster.
regulation of calcineurin-NFAT signaling cascade Any process that modulates the frequency, rate or extent of the calcineurin-NFAT signaling cascade.
regulation of circadian rhythm Any process that modulates the frequency, rate or extent of a circadian rhythm. A circadian rhythm is a biological process in an organism that recurs with a regularity of approximately 24 hours.
regulation of microtubule cytoskeleton organization Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising microtubules and their associated proteins.
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 protein import into nucleus Any process that modulates the frequency, rate or extent of movement of proteins from the cytoplasm to the nucleus.
regulation of proteolysis Any process that modulates the frequency, rate or extent of the hydrolysis of a peptide bond or bonds within a protein.
response to anesthetic 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 anesthetic stimulus. An anesthetic is a substance that causes loss of feeling, awareness, or sensation.
rhythmic behavior The specific behavior of an organism that recur with measured regularity.
segment polarity determination Division of the 14 parasegments of the embryo into anterior and posterior compartments; exemplified by the actions of the segment polarity gene products.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
somatic stem cell population maintenance Any process by which an organism retains a population of somatic stem cells, undifferentiated cells in the embryo or adult which can undergo unlimited division and give rise to cell types of the body other than those of the germ-line.
spindle organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the spindle, the array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during DNA segregation and serves to move the duplicated chromosomes apart.
synaptic assembly at neuromuscular junction The assembly of a synapse at a neuromuscular junction.
wing and notum subfield formation The regionalization process that subdivides the wing imaginal disc into the wing and notum (body wall) subfields, thus determining whether cells ultimately differentiate wing or notum-specific structures.

11 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P49841 GSK3B Glycogen synthase kinase-3 beta Homo sapiens (Human) EV
P49840 GSK3A Glycogen synthase kinase-3 alpha Homo sapiens (Human) PR
Q80YS9 Stkld1 Serine/threonine kinase-like domain-containing protein STKLD1 Mus musculus (Mouse) PR
Q2NL51 Gsk3a Glycogen synthase kinase-3 alpha Mus musculus (Mouse) SS
Q9WV60 Gsk3b Glycogen synthase kinase-3 beta Mus musculus (Mouse) EV
P18266 Gsk3b Glycogen synthase kinase-3 beta Rattus norvegicus (Rat) PR
P18265 Gsk3a Glycogen synthase kinase-3 alpha Rattus norvegicus (Rat) PR
Q09595 R03D7.5 Putative serine/threonine-protein kinase R03D7.5 Caenorhabditis elegans PR
Q9U2Q9 gsk-3 Glycogen synthase kinase-3 Caenorhabditis elegans PR
Q39019 ASK10 Shaggy-related protein kinase kappa Arabidopsis thaliana (Mouse-ear cress) PR
Q9FVS6 ASK4 Shaggy-related protein kinase delta Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MSGRPRTSSF AEGNKQSPSL VLGGVKTCSR DGSKITTVVA TPGQGTDRVQ EVSYTDTKVI
70 80 90 100 110 120
GNGSFGVVFQ AKLCDTGELV AIKKVLQDRR FKNRELQIMR KLEHCNIVKL LYFFYSSGEK
130 140 150 160 170 180
RDEVFLNLVL EYIPETVYKV ARQYAKTKQT IPINFIRLYM YQLFRSLAYI HSLGICHRDI
190 200 210 220 230 240
KPQNLLLDPE TAVLKLCDFG SAKQLLHGEP NVSYICSRYY RAPELIFGAI NYTTKIDVWS
250 260 270 280 290 300
AGCVLAELLL GQPIFPGDSG VDQLVEVIKV LGTPTREQIR EMNPNYTEFK FPQIKSHPWQ
310 320 330 340 350 360
KVFRIRTPTE AINLVSLLLE YTPSARITPL KACAHPFFDE LRMEGNHTLP NGRDMPPLFN
370 380 390 400 410 420
FTEHELSIQP SLVPQLLPKH LQNASGPGGN RPSAGGAASI AASGSTSVSS TGSGASVEGS
430 440 450 460 470 480
AQPQSQGTAA AAGSGSGGAT AGTGGASAGG PGSGNNSSSG GASGAPSAVA AGGANAAVAG
490 500 510
GAGGGGGAGA ATAAATATGA IGATNAGGAN VTDS