| Tag | Content |
|---|---|
| Uniprot ID | Q9WV60 |
| Entrez ID | 56637 |
| Genbank protein ID | AAH06936.1; AAD39258.2; AAH60743.1; |
| Genbank nucleotide ID | NM_019827.6 |
| Ensembl protein ID | ENSMUSP00000023507 |
| Ensembl nucleotide ID | ENSMUSG00000022812 |
| Gene name | Glycogen synthase kinase-3 beta |
| Gene symbol | Gsk3b |
| Organism | Mus musculus |
| NCBI taxa ID | 10090 |
| Cleft type | CPO |
| Developmental stage | E12.5, E13.5, E14.5, P6 |
| Data sources | Manually collected |
| Reference | 14690613; 20981831; 17293880; |
| Functional description | Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-679' upon T-cell activation. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2 (PubMed:20049328, PubMed:28903391). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (By similarity). Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:20049328, PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression (PubMed:28556462). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:22539723). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity). |
| Sequence | MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR PQEVSYTDTK 60 VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI MRKLDHCNIV RLRYFFYSSG 120 EKKDEVYLNL VLDYVPETVY RVARHYSRAK QTLPVIYVKL YMYQLFRSLA YIHSFGICHR 180 DIKPQNLLLD PDTAVLKLCD FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV 240 WSAGCVLAEL LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP 300 WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL PNGRDTPALF 360 NFTTQELSSN PPLATILIPP HARIQAAASP PANATAASDT NAGDRGQTNN AASASASNST 420 |
Abbreviation :
CLO : cleft lip only. CPO : cleft palate only.
CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.
| Relation | Gene symbol | Entrez ID | UniProt ID | Cleft type | Developmental stage | Species | Evidence | Details |
|---|---|---|---|---|---|---|---|---|
| 1:1 ortholog | GSK3B | 478575 | E2RB53 | Canis lupus familiaris | Prediction | More>> | ||
| 1:1 ortholog | GSK3B1 | 102176363 | A0A097P8R4 | Capra hircus | Prediction | More>> | ||
| 1:1 ortholog | GSK3B | 2932 | P49841 | Homo sapiens | Prediction | More>> | ||
| 1:1 ortholog | Gsk3b | 56637 | Q9WV60 | CPO | E12.5, E13.5, E14.5, P6 | Mus musculus | Publication | More>> |
| 1:1 ortholog | GSK3B | 100616510 | K7CFX8 | Pan troglodytes | Prediction | More>> | ||
| 1:1 ortholog | GSK3B | I6ZJZ7 | Sus scrofa | Prediction | More>> | |||
| 1:1 ortholog | GSK3B | 100348842 | A0A5F9CM08 | Oryctolagus cuniculus | Prediction | More>> | ||
| 1:1 ortholog | Gsk3b | 84027 | A0A0G2KB98 | Rattus norvegicus | Prediction | More>> | ||
| 1:1 ortholog | gsk3ba | 30654 | Q9YH60 | Danio rerio | Prediction | More>> |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0001085 | RNA polymerase II transcription factor binding | ISO |
| GO:0002020 | protease binding | ISO |
| GO:0002039 | p53 binding | ISO |
| GO:0004672 | protein kinase activity | ISO |
| GO:0004672 | protein kinase activity | IDA |
| GO:0004674 | protein serine/threonine kinase activity | ISO |
| GO:0004674 | protein serine/threonine kinase activity | ISS |
| GO:0004674 | protein serine/threonine kinase activity | IDA |
| GO:0004674 | protein serine/threonine kinase activity | IMP |
| GO:0004674 | protein serine/threonine kinase activity | IBA |
| GO:0004674 | protein serine/threonine kinase activity | TAS |
| GO:0005178 | integrin binding | ISO |
| GO:0005515 | protein binding | IPI |
| GO:0005524 | ATP binding | ISO |
| GO:0008013 | beta-catenin binding | ISO |
| GO:0008013 | beta-catenin binding | IPI |
| GO:0008013 | beta-catenin binding | IBA |
| GO:0008134 | transcription factor binding | ISO |
| GO:0016301 | kinase activity | ISS |
| GO:0016301 | kinase activity | ISO |
| GO:0019901 | protein kinase binding | ISO |
| GO:0019901 | protein kinase binding | IPI |
| GO:0031625 | ubiquitin protein ligase binding | ISO |
| GO:0034236 | protein kinase A catalytic subunit binding | ISO |
| GO:0034452 | dynactin binding | ISO |
| GO:0035255 | ionotropic glutamate receptor binding | ISO |
| GO:0048156 | tau protein binding | ISO |
| GO:0050321 | tau-protein kinase activity | ISO |
| GO:0050321 | tau-protein kinase activity | IDA |
| GO:0050321 | tau-protein kinase activity | IBA |
| GO:0051059 | NF-kappaB binding | ISO |
| GO:0070840 | dynein complex binding | IPI |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0000320 | re-entry into mitotic cell cycle | IDA |
| GO:0001558 | regulation of cell growth | IMP |
| GO:0001837 | epithelial to mesenchymal transition | ISS |
| GO:0001837 | epithelial to mesenchymal transition | ISO |
| GO:0001954 | positive regulation of cell-matrix adhesion | ISO |
| GO:0005977 | glycogen metabolic process | ISO |
| GO:0006349 | regulation of gene expression by genetic imprinting | IMP |
| GO:0006468 | protein phosphorylation | ISO |
| GO:0006468 | protein phosphorylation | IDA |
| GO:0006468 | protein phosphorylation | IMP |
| GO:0006468 | protein phosphorylation | IGI |
| GO:0006611 | protein export from nucleus | IDA |
| GO:0006983 | ER overload response | ISO |
| GO:0006983 | ER overload response | IDA |
| GO:0007010 | cytoskeleton organization | TAS |
| GO:0007163 | establishment or maintenance of cell polarity | ISO |
| GO:0007165 | signal transduction | IBA |
| GO:0007409 | axonogenesis | IGI |
| GO:0007520 | myoblast fusion | IDA |
| GO:0007520 | myoblast fusion | IGI |
| GO:0007623 | circadian rhythm | IMP |
| GO:0008286 | insulin receptor signaling pathway | IBA |
| GO:0008286 | insulin receptor signaling pathway | IDA |
| GO:0009887 | animal organ morphogenesis | IMP |
| GO:0010043 | response to zinc ion | ISO |
| GO:0010508 | positive regulation of autophagy | IDA |
| GO:0010508 | positive regulation of autophagy | IGI |
| GO:0010614 | negative regulation of cardiac muscle hypertrophy | IDA |
| GO:0010628 | positive regulation of gene expression | IGI |
| GO:0010628 | positive regulation of gene expression | IMP |
| GO:0010800 | positive regulation of peptidyl-threonine phosphorylation | IDA |
| GO:0010822 | positive regulation of mitochondrion organization | ISO |
| GO:0010918 | positive regulation of mitochondrial membrane potential | ISO |
| GO:0010975 | regulation of neuron projection development | IBA |
| GO:0010975 | regulation of neuron projection development | IGI |
| GO:0010977 | negative regulation of neuron projection development | IGI |
| GO:0010977 | negative regulation of neuron projection development | IMP |
| GO:0014043 | negative regulation of neuron maturation | IGI |
| GO:0014902 | myotube differentiation | IGI |
| GO:0016055 | Wnt signaling pathway | IGI |
| GO:0016310 | phosphorylation | IMP |
| GO:0016477 | cell migration | IGI |
| GO:0018105 | peptidyl-serine phosphorylation | ISO |
| GO:0018105 | peptidyl-serine phosphorylation | IGI |
| GO:0018105 | peptidyl-serine phosphorylation | IDA |
| GO:0018107 | peptidyl-threonine phosphorylation | ISO |
| GO:0021766 | hippocampus development | ISO |
| GO:0030010 | establishment of cell polarity | ISO |
| GO:0030011 | maintenance of cell polarity | ISO |
| GO:0030516 | regulation of axon extension | ISO |
| GO:0031175 | neuron projection development | ISS |
| GO:0031175 | neuron projection development | ISO |
| GO:0031333 | negative regulation of protein-containing complex assembly | ISO |
| GO:0031334 | positive regulation of protein-containing complex assembly | ISO |
| GO:0032007 | negative regulation of TOR signaling | IGI |
| GO:0032091 | negative regulation of protein binding | ISO |
| GO:0032092 | positive regulation of protein binding | IDA |
| GO:0032436 | positive regulation of proteasomal ubiquitin-dependent protein catabolic process | ISO |
| GO:0032436 | positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IGI |
| GO:0032886 | regulation of microtubule-based process | ISO |
| GO:0032886 | regulation of microtubule-based process | IDA |
| GO:0033690 | positive regulation of osteoblast proliferation | ISO |
| GO:0034392 | negative regulation of smooth muscle cell apoptotic process | ISO |
| GO:0035372 | protein localization to microtubule | IGI |
| GO:0035556 | intracellular signal transduction | ISO |
| GO:0035729 | cellular response to hepatocyte growth factor stimulus | IDA |
| GO:0035733 | hepatic stellate cell activation | ISO |
| GO:0036016 | cellular response to interleukin-3 | IDA |
| GO:0042752 | regulation of circadian rhythm | IMP |
| GO:0042981 | regulation of apoptotic process | IMP |
| GO:0043065 | positive regulation of apoptotic process | ISO |
| GO:0043066 | negative regulation of apoptotic process | ISO |
| GO:0043066 | negative regulation of apoptotic process | IMP |
| GO:0043407 | negative regulation of MAP kinase activity | ISO |
| GO:0043525 | positive regulation of neuron apoptotic process | ISO |
| GO:0043547 | positive regulation of GTPase activity | ISO |
| GO:0044027 | hypermethylation of CpG island | IMP |
| GO:0045444 | fat cell differentiation | IDA |
| GO:0045667 | regulation of osteoblast differentiation | ISO |
| GO:0045672 | positive regulation of osteoclast differentiation | ISO |
| GO:0045732 | positive regulation of protein catabolic process | ISO |
| GO:0045773 | positive regulation of axon extension | IGI |
| GO:0045944 | positive regulation of transcription by RNA polymerase II | IMP |
| GO:0046777 | protein autophosphorylation | ISO |
| GO:0046827 | positive regulation of protein export from nucleus | ISO |
| GO:0046849 | bone remodeling | ISO |
| GO:0048168 | regulation of neuronal synaptic plasticity | ISO |
| GO:0048661 | positive regulation of smooth muscle cell proliferation | ISO |
| GO:0048814 | regulation of dendrite morphogenesis | ISO |
| GO:0050770 | regulation of axonogenesis | ISO |
| GO:0050774 | negative regulation of dendrite morphogenesis | ISO |
| GO:0051001 | negative regulation of nitric-oxide synthase activity | ISO |
| GO:0060070 | canonical Wnt signaling pathway | IDA |
| GO:0060070 | canonical Wnt signaling pathway | IGI |
| GO:0061049 | cell growth involved in cardiac muscle cell development | ISO |
| GO:0070059 | intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | IDA |
| GO:0070507 | regulation of microtubule cytoskeleton organization | ISO |
| GO:0070507 | regulation of microtubule cytoskeleton organization | IBA |
| GO:0070885 | negative regulation of calcineurin-NFAT signaling cascade | ISS |
| GO:0070885 | negative regulation of calcineurin-NFAT signaling cascade | ISO |
| GO:0071109 | superior temporal gyrus development | ISO |
| GO:0071260 | cellular response to mechanical stimulus | ISO |
| GO:0090090 | negative regulation of canonical Wnt signaling pathway | IMP |
| GO:0090090 | negative regulation of canonical Wnt signaling pathway | IBA |
| GO:0090290 | positive regulation of osteoclast proliferation | ISO |
| GO:0097191 | extrinsic apoptotic signaling pathway | IGI |
| GO:0097192 | extrinsic apoptotic signaling pathway in absence of ligand | IDA |
| GO:0097192 | extrinsic apoptotic signaling pathway in absence of ligand | IBA |
| GO:0097284 | hepatocyte apoptotic process | ISO |
| GO:0098696 | regulation of neurotransmitter receptor localization to postsynaptic specialization membrane | ISO |
| GO:0099159 | regulation of modification of postsynaptic structure | ISO |
| GO:0106027 | neuron projection organization | ISO |
| GO:0150101 | regulation of microtubule anchoring at centrosome | ISO |
| GO:1900181 | negative regulation of protein localization to nucleus | ISO |
| GO:1900271 | regulation of long-term synaptic potentiation | IMP |
| GO:1901030 | positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway | IDA |
| GO:1901215 | negative regulation of neuron death | ISS |
| GO:1901215 | negative regulation of neuron death | ISO |
| GO:1901216 | positive regulation of neuron death | ISO |
| GO:1901984 | negative regulation of protein acetylation | ISO |
| GO:1902042 | negative regulation of extrinsic apoptotic signaling pathway via death domain receptors | ISS |
| GO:1902042 | negative regulation of extrinsic apoptotic signaling pathway via death domain receptors | ISO |
| GO:1904339 | negative regulation of dopaminergic neuron differentiation | ISO |
| GO:1904646 | cellular response to amyloid-beta | ISO |
| GO:1904780 | negative regulation of protein localization to centrosome | IMP |
| GO:1904781 | positive regulation of protein localization to centrosome | ISO |
| GO:2000171 | negative regulation of dendrite development | ISO |
| GO:2000300 | regulation of synaptic vesicle exocytosis | ISO |
| GO:2000463 | positive regulation of excitatory postsynaptic potential | ISO |
| GO:2000573 | positive regulation of DNA biosynthetic process | ISO |
| GO:2000727 | positive regulation of cardiac muscle cell differentiation | IMP |
| GO:2000738 | positive regulation of stem cell differentiation | IMP |
| GO:2001223 | negative regulation of neuron migration | ISO |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0005634 | nucleus | ISO |
| GO:0005634 | nucleus | ISS |
| GO:0005634 | nucleus | IDA |
| GO:0005634 | nucleus | IBA |
| GO:0005654 | nucleoplasm | ISO |
| GO:0005654 | nucleoplasm | TAS |
| GO:0005737 | cytoplasm | ISO |
| GO:0005737 | cytoplasm | ISS |
| GO:0005737 | cytoplasm | IBA |
| GO:0005739 | mitochondrion | ISO |
| GO:0005813 | centrosome | ISO |
| GO:0005829 | cytosol | ISO |
| GO:0005829 | cytosol | IDA |
| GO:0005829 | cytosol | IBA |
| GO:0005829 | cytosol | TAS |
| GO:0005874 | microtubule | ISO |
| GO:0005886 | plasma membrane | ISS |
| GO:0005886 | plasma membrane | ISO |
| GO:0014069 | postsynaptic density | IDA |
| GO:0016020 | membrane | ISS |
| GO:0016020 | membrane | ISO |
| GO:0030424 | axon | ISO |
| GO:0030424 | axon | IBA |
| GO:0030425 | dendrite | ISO |
| GO:0030426 | growth cone | IDA |
| GO:0030877 | beta-catenin destruction complex | ISO |
| GO:0030877 | beta-catenin destruction complex | IDA |
| GO:0030877 | beta-catenin destruction complex | IBA |
| GO:0032991 | protein-containing complex | ISO |
| GO:0043025 | neuronal cell body | IDA |
| GO:0043197 | dendritic spine | ISO |
| GO:0043198 | dendritic shaft | IDA |
| GO:0043227 | membrane-bounded organelle | IDA |
| GO:0044297 | cell body | IDA |
| GO:0045121 | membrane raft | ISO |
| GO:0048471 | perinuclear region of cytoplasm | IDA |
| GO:0098685 | Schaffer collateral - CA1 synapse | ISO |
| GO:0098978 | glutamatergic synapse | ISO |
| GO:0098978 | glutamatergic synapse | IDA |
| GO:0098978 | glutamatergic synapse | IBA |
| GO:1990904 | ribonucleoprotein complex | IDA |
| GO:1990909 | Wnt signalosome | IDA |
| Reactome ID | Reactome Term | Evidence |
|---|---|---|
| R-MMU-1266738 | Developmental Biology | IEA |
| R-MMU-162582 | Signal Transduction | IEA |
| R-MMU-195253 | Degradation of beta-catenin by the destruction complex | IEA |
| R-MMU-195721 | Signaling by WNT | IEA |
| R-MMU-196299 | Beta-catenin phosphorylation cascade | IEA |
| R-MMU-201681 | TCF dependent signaling in response to WNT | IEA |
| R-MMU-212165 | Epigenetic regulation of gene expression | IEA |
| R-MMU-2262752 | Cellular responses to stress | IEA |
| R-MMU-3371453 | Regulation of HSF1-mediated heat shock response | IEA |
| R-MMU-3371556 | Cellular response to heat stress | IEA |
| R-MMU-373755 | Semaphorin interactions | IEA |
| R-MMU-399956 | CRMPs in Sema3A signaling | IEA |
| R-MMU-422475 | Axon guidance | IEA |
| R-MMU-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | IEA |
| R-MMU-5250913 | Positive epigenetic regulation of rRNA expression | IEA |
| R-MMU-5250924 | B-WICH complex positively regulates rRNA expression | IEA |
| R-MMU-5358351 | Signaling by Hedgehog | IEA |
| R-MMU-5610785 | GLI3 is processed to GLI3R by the proteasome | IEA |
| R-MMU-5610787 | Hedgehog 'off' state | IEA |
| R-MMU-74160 | Gene expression (Transcription) | IEA |
| R-MMU-8953897 | Cellular responses to external stimuli | IEA |
| Keyword ID | Keyword Term |
|---|---|
| KW-0002 | 3D-structure |
| KW-0013 | ADP-ribosylation |
| KW-0067 | ATP-binding |
| KW-0090 | Biological rhythms |
| KW-0119 | Carbohydrate metabolism |
| KW-1003 | Cell membrane |
| KW-0963 | Cytoplasm |
| KW-0217 | Developmental protein |
| KW-0221 | Differentiation |
| KW-0321 | Glycogen metabolism |
| KW-0418 | Kinase |
| KW-0472 | Membrane |
| KW-0524 | Neurogenesis |
| KW-0547 | Nucleotide-binding |
| KW-0539 | Nucleus |
| KW-0597 | Phosphoprotein |
| KW-1185 | Reference proteome |
| KW-0723 | Serine/threonine-protein kinase |
| KW-0734 | Signal transduction inhibitor |
| KW-0808 | Transferase |
| KW-0879 | Wnt signaling pathway |
| Pfam ID | Pfam Term |
|---|---|
| PF00069 | Pkinase |