GSK3B (glycogen synthase kinase 3 beta)

Gene

• Entrez ID: 2932
• Gene name: Glycogen synthase kinase 3 beta
• Gene symbol: GSK3B
• Synonyms: -
• Chromosome: 3
• Chromosome location: 3q13.33
• Summary: The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004676	hsa-miR-26a-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	20525681
MIRT004676	hsa-miR-26a-5p	Immunoblot, Immunofluorescence, Immunoprecipitaion, Luciferase reporter assay, qRT-PCR	22484120
MIRT004676	hsa-miR-26a-5p	PAR-CLIP	21572407
MIRT004676	hsa-miR-26a-5p	PAR-CLIP	20371350
MIRT004676	hsa-miR-26a-5p	Luciferase reporter assay	26854694
MIRT004676	hsa-miR-26a-5p	Luciferase reporter assay	26893786
MIRT004676	hsa-miR-26a-5p	Luciferase reporter assay, Western blot	28237093
MIRT004676	hsa-miR-26a-5p	Immunofluorescence, Immunoprecipitaion, Luciferase reporter assay, qRT-PCR, Western blot	26469406
MIRT004676	hsa-miR-26a-5p	Luciferase reporter assay	26313916
MIRT006753	hsa-miR-29b-3p	Luciferase reporter assay	21501592
MIRT021044	hsa-miR-155-5p	Proteomics	19289835
MIRT036842	hsa-miR-877-3p	CLASH	23622248
MIRT039319	hsa-miR-425-5p	CLASH	23622248
MIRT049345	hsa-miR-92a-3p	CLASH	23622248
MIRT053782	hsa-miR-183-5p	Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	24335145
MIRT053783	hsa-miR-96-5p	Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	24335145
MIRT053784	hsa-miR-182-5p	Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	24335145
MIRT120263	hsa-let-7a-3p	PAR-CLIP	20371350
MIRT120264	hsa-let-7b-3p	PAR-CLIP	20371350
MIRT120265	hsa-let-7f-1-3p	PAR-CLIP	20371350
MIRT120266	hsa-let-7f-2-3p	PAR-CLIP	21572407
MIRT120266	hsa-let-7f-2-3p	PAR-CLIP	20371350
MIRT120267	hsa-miR-98-3p	PAR-CLIP	20371350
MIRT120269	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT120269	hsa-miR-190a-3p	PAR-CLIP	22012620
MIRT120269	hsa-miR-190a-3p	PAR-CLIP	21572407
MIRT120269	hsa-miR-190a-3p	HITS-CLIP	23313552
MIRT120272	hsa-miR-1185-2-3p	PAR-CLIP	21572407
MIRT120272	hsa-miR-1185-2-3p	PAR-CLIP	20371350
MIRT120273	hsa-miR-1185-1-3p	PAR-CLIP	21572407
MIRT120273	hsa-miR-1185-1-3p	PAR-CLIP	20371350
MIRT120275	hsa-miR-4789-5p	PAR-CLIP	21572407
MIRT120275	hsa-miR-4789-5p	PAR-CLIP	20371350
MIRT120276	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT120276	hsa-miR-5011-5p	PAR-CLIP	22012620
MIRT120276	hsa-miR-5011-5p	PAR-CLIP	21572407
MIRT120276	hsa-miR-5011-5p	HITS-CLIP	23313552
MIRT437488	hsa-miR-346	Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blot	24023731
MIRT438593	hsa-miR-199a-5p	ChIP-seq, FACS, Immunofluorescence, Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23764775
MIRT440532	hsa-miR-409-5p	HITS-CLIP	24374217
MIRT504732	hsa-miR-1277-5p	PAR-CLIP	23446348
MIRT504732	hsa-miR-1277-5p	PAR-CLIP	22012620
MIRT504732	hsa-miR-1277-5p	PAR-CLIP	21572407
MIRT504732	hsa-miR-1277-5p	HITS-CLIP	23313552
MIRT504733	hsa-miR-374b-5p	PAR-CLIP	23446348
MIRT504733	hsa-miR-374b-5p	PAR-CLIP	22012620
MIRT504733	hsa-miR-374b-5p	PAR-CLIP	21572407
MIRT504733	hsa-miR-374b-5p	HITS-CLIP	23313552
MIRT504734	hsa-miR-374a-5p	PAR-CLIP	23446348
MIRT504734	hsa-miR-374a-5p	PAR-CLIP	22012620
MIRT504734	hsa-miR-374a-5p	PAR-CLIP	21572407
MIRT504734	hsa-miR-374a-5p	HITS-CLIP	23313552
MIRT504735	hsa-miR-410-3p	PAR-CLIP	23446348
MIRT504735	hsa-miR-410-3p	PAR-CLIP	22012620
MIRT504735	hsa-miR-410-3p	PAR-CLIP	21572407
MIRT504735	hsa-miR-410-3p	HITS-CLIP	23313552
MIRT504736	hsa-miR-5692c	PAR-CLIP	23446348
MIRT504736	hsa-miR-5692c	PAR-CLIP	22012620
MIRT504736	hsa-miR-5692c	PAR-CLIP	21572407
MIRT504736	hsa-miR-5692c	HITS-CLIP	23313552
MIRT504737	hsa-miR-5692b	PAR-CLIP	23446348
MIRT504737	hsa-miR-5692b	PAR-CLIP	22012620
MIRT504737	hsa-miR-5692b	PAR-CLIP	21572407
MIRT504737	hsa-miR-5692b	HITS-CLIP	23313552
MIRT504738	hsa-miR-513c-3p	PAR-CLIP	23446348
MIRT504738	hsa-miR-513c-3p	PAR-CLIP	22012620
MIRT504738	hsa-miR-513c-3p	PAR-CLIP	21572407
MIRT504738	hsa-miR-513c-3p	HITS-CLIP	23313552
MIRT504739	hsa-miR-369-3p	PAR-CLIP	23446348
MIRT504739	hsa-miR-369-3p	PAR-CLIP	22012620
MIRT504739	hsa-miR-369-3p	PAR-CLIP	21572407
MIRT504739	hsa-miR-369-3p	HITS-CLIP	23313552
MIRT504740	hsa-miR-513a-3p	PAR-CLIP	23446348
MIRT504740	hsa-miR-513a-3p	PAR-CLIP	22012620
MIRT504740	hsa-miR-513a-3p	PAR-CLIP	21572407
MIRT504740	hsa-miR-513a-3p	HITS-CLIP	23313552
MIRT504741	hsa-miR-3606-3p	PAR-CLIP	23446348
MIRT504741	hsa-miR-3606-3p	PAR-CLIP	22012620
MIRT504741	hsa-miR-3606-3p	PAR-CLIP	21572407
MIRT504741	hsa-miR-3606-3p	HITS-CLIP	23313552
MIRT523376	hsa-miR-6083	PAR-CLIP	23446348
MIRT523376	hsa-miR-6083	PAR-CLIP	21572407
MIRT523376	hsa-miR-6083	HITS-CLIP	23313552
MIRT557458	hsa-miR-4465	PAR-CLIP	21572407
MIRT557458	hsa-miR-4465	PAR-CLIP	20371350
MIRT557459	hsa-miR-26b-5p	PAR-CLIP	21572407
MIRT557459	hsa-miR-26b-5p	PAR-CLIP	20371350
MIRT557460	hsa-miR-1297	PAR-CLIP	21572407
MIRT557460	hsa-miR-1297	PAR-CLIP	20371350
MIRT557461	hsa-miR-5697	PAR-CLIP	21572407
MIRT557461	hsa-miR-5697	PAR-CLIP	20371350
MIRT557462	hsa-miR-5683	PAR-CLIP	21572407
MIRT557462	hsa-miR-5683	PAR-CLIP	20371350
MIRT557463	hsa-miR-33a-3p	PAR-CLIP	21572407
MIRT557463	hsa-miR-33a-3p	PAR-CLIP	20371350
MIRT557464	hsa-miR-409-3p	PAR-CLIP	21572407
MIRT557464	hsa-miR-409-3p	PAR-CLIP	20371350
MIRT557465	hsa-miR-1910-5p	PAR-CLIP	21572407
MIRT557465	hsa-miR-1910-5p	HITS-CLIP	23313552
MIRT611910	hsa-miR-8064	HITS-CLIP	23824327
MIRT611910	hsa-miR-8064	HITS-CLIP	27418678
MIRT611911	hsa-miR-4643	HITS-CLIP	23824327
MIRT611911	hsa-miR-4643	HITS-CLIP	27418678
MIRT611912	hsa-miR-8485	HITS-CLIP	23824327
MIRT629076	hsa-miR-383-3p	HITS-CLIP	23824327
MIRT629077	hsa-miR-3065-3p	HITS-CLIP	23824327
MIRT657555	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT657556	hsa-miR-6787-3p	HITS-CLIP	23824327
MIRT657557	hsa-miR-548c-3p	HITS-CLIP	23824327
MIRT727520	hsa-miR-16-5p	HITS-CLIP	22473208
MIRT727521	hsa-miR-195-5p	HITS-CLIP	22473208
MIRT727522	hsa-miR-15b-5p	HITS-CLIP	22473208
MIRT727523	hsa-miR-15a-5p	HITS-CLIP	22473208
MIRT731560	hsa-miR-9-5p	Luciferase reporter assay	26891291
MIRT731812	hsa-miR-769-5p	Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blot	27470346
MIRT731878	hsa-miR-27a-3p	ChIP, Luciferase reporter assay, qRT-PCR, Western blot	28122350
MIRT732723	hsa-miR-129-1-3p	Luciferase reporter assay	27050373
MIRT732796	hsa-miR-99b-3p	Luciferase reporter assay, qRT-PCR, Western blot	26315788
MIRT732939	hsa-miR-29a-3p	qRT-PCR, Western blot	27523474
MIRT733093	hsa-miR-26a-1-3p	Luciferase reporter assay, qRT-PCR, Western blot	25961460
MIRT733572	hsa-miR-501-5p	Luciferase reporter assay, qRT-PCR, Western blot	27846906
MIRT733592	hsa-miR-616-5p	Luciferase reporter assay	27890917
MIRT733922	hsa-miR-1246	Immunofluorescence, Luciferase reporter assay, qRT-PCR	27639189
MIRT734436	hsa-miR-942-5p	Luciferase reporter assay, Western blot	25844602
MIRT734689	hsa-miR-224-5p	Luciferase reporter assay	25588771
MIRT735176	hsa-miR-29a-5p	Luciferase reporter assay, qRT-PCR, Western blot	25846459
MIRT735406	hsa-miR-744-5p	Western blot	28107193
MIRT784132	hsa-miR-203a-3p	HITS-CLIP	27418678

Transcription factors

Transcription factor	Regulation	Reference
CDX2	Unknown	24501326
CREB1	Unknown	11579131
NFKB1	Unknown	11579131
TFCP2	Unknown	16973241

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001085	Function	RNA polymerase II transcription factor binding	IPI	20864106
GO:0001837	Process	Epithelial to mesenchymal transition	IMP	15448698
GO:0001954	Process	Positive regulation of cell-matrix adhesion	IMP	18156211
GO:0002020	Function	Protease binding	IPI	25118933
GO:0002039	Function	P53 binding	IDA	14744935
GO:0004672	Function	Protein kinase activity	IMP	16981698
GO:0004672	Function	Protein kinase activity	TAS	22988876, 24115276, 26049140
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	8638126, 9072970, 11035810, 11104755, 11955436, 14744935, 16315267, 17139249, 18348280, 19364825
GO:0004674	Function	Protein serine/threonine kinase activity	IMP	16981698
GO:0004674	Function	Protein serine/threonine kinase activity	ISS
GO:0004674	Function	Protein serine/threonine kinase activity	NAS	8725894, 28386764
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0005515	Function	Protein binding	IPI	8638126, 9482734, 9601641, 9731200, 10481074, 11004522, 11035810, 11738041, 12421363, 12434148, 12927815, 14744935, 15147888, 15448698, 15752768, 16282323, 16365045, 16890161, 16981698, 17078951, 17139249, 17317006, 17318191, 17510365, 17601533, 18045539, 18505846, 18687691, 1884611
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	14744935, 15448698
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	14744935, 15448698, 18787224, 19038973, 20937854
GO:0005739	Component	Mitochondrion	IEA
GO:0005813	Component	Centrosome	IDA	17139249, 21399614
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	20937854
GO:0005977	Process	Glycogen metabolic process	IDA	8638126
GO:0006468	Process	Protein phosphorylation	IDA	11035810, 16315267, 20937854
GO:0006468	Process	Protein phosphorylation	IMP	16981698
GO:0006468	Process	Protein phosphorylation	TAS	26049140
GO:0006983	Process	ER overload response	IDA	14744935
GO:0007165	Process	Signal transduction	IBA	21873635
GO:0007212	Process	Dopamine receptor signaling pathway	NAS	21711983
GO:0007623	Process	Circadian rhythm	ISS
GO:0008013	Function	Beta-catenin binding	IBA	21873635
GO:0008013	Function	Beta-catenin binding	IPI	8638126
GO:0008286	Process	Insulin receptor signaling pathway	IBA	21873635
GO:0010508	Process	Positive regulation of autophagy	ISS
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0010822	Process	Positive regulation of mitochondrion organization	IMP	25118933
GO:0010975	Process	Regulation of neuron projection development	IBA	21873635
GO:0016055	Process	Wnt signaling pathway	TAS
GO:0016301	Function	Kinase activity	IDA	15448698, 24391509
GO:0016301	Function	Kinase activity	TAS
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	8638126, 11104755, 11955436, 14744935, 17139249
GO:0018107	Process	Peptidyl-threonine phosphorylation	IDA	11955436, 17139249, 25897075
GO:0019901	Function	Protein kinase binding	IPI	18348280
GO:0021766	Process	Hippocampus development	IMP	19581563
GO:0030010	Process	Establishment of cell polarity	ISS
GO:0030010	Process	Establishment of cell polarity	TAS	18268107
GO:0030011	Process	Maintenance of cell polarity	ISS
GO:0030011	Process	Maintenance of cell polarity	TAS	18268107
GO:0030424	Component	Axon	IBA	21873635
GO:0030424	Component	Axon	ISS
GO:0030425	Component	Dendrite	ISS
GO:0030516	Process	Regulation of axon extension	ISS
GO:0030877	Component	Beta-catenin destruction complex	IBA	21873635
GO:0030877	Component	Beta-catenin destruction complex	IDA	8638126, 9601641, 16188939
GO:0030877	Component	Beta-catenin destruction complex	TAS	11955436, 19366350
GO:0031175	Process	Neuron projection development	IDA	19830702
GO:0031333	Process	Negative regulation of protein-containing complex assembly	IMP	16188939
GO:0031334	Process	Positive regulation of protein-containing complex assembly	IDA	8638126
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	21118991
GO:0032091	Process	Negative regulation of protein binding	IDA	16890161
GO:0032092	Process	Positive regulation of protein binding	ISS
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IC	11955436
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IDA	19364825
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP	25897075
GO:0032515	Process	Negative regulation of phosphoprotein phosphatase activity	TAS	28386764
GO:0032886	Process	Regulation of microtubule-based process	IMP	20937854
GO:0034236	Function	Protein kinase A catalytic subunit binding	IPI	11035810
GO:0034452	Function	Dynactin binding	IPI	17139249
GO:0035556	Process	Intracellular signal transduction	IDA	14749367
GO:0035556	Process	Intracellular signal transduction	TAS	26049140
GO:0036016	Process	Cellular response to interleukin-3	ISS
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0043066	Process	Negative regulation of apoptotic process	IDA	14744935
GO:0043547	Process	Positive regulation of GTPase activity	IMP	18156211
GO:0045719	Process	Negative regulation of glycogen biosynthetic process	TAS	19366350
GO:0045732	Process	Positive regulation of protein catabolic process	IC	16188939
GO:0046777	Process	Protein autophosphorylation	IDA	23184662
GO:0046827	Process	Positive regulation of protein export from nucleus	IDA	14744935
GO:0048156	Function	Tau protein binding	NAS	28386764
GO:0048814	Process	Regulation of dendrite morphogenesis	ISS
GO:0050321	Function	Tau-protein kinase activity	IBA	21873635
GO:0050321	Function	Tau-protein kinase activity	IDA	14690523, 16365045
GO:0050321	Function	Tau-protein kinase activity	NAS	28386764
GO:0050770	Process	Regulation of axonogenesis	ISS
GO:0051059	Function	NF-kappaB binding	IPI	15465828
GO:0060079	Process	Excitatory postsynaptic potential	NAS	21711983
GO:0070507	Process	Regulation of microtubule cytoskeleton organization	IBA	21873635
GO:0070507	Process	Regulation of microtubule cytoskeleton organization	ISS
GO:0070885	Process	Negative regulation of calcineurin-NFAT signaling cascade	IMP	9072970
GO:0071109	Process	Superior temporal gyrus development	IMP	19581563
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IBA	21873635
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IC	9601641, 11955436
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	ISS
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	TAS	19366350
GO:0097191	Process	Extrinsic apoptotic signaling pathway	ISS
GO:0097192	Process	Extrinsic apoptotic signaling pathway in absence of ligand	IBA	21873635
GO:0097192	Process	Extrinsic apoptotic signaling pathway in absence of ligand	ISS
GO:0098794	Component	Postsynapse	IEA
GO:0098978	Component	Glutamatergic synapse	EXP	17989287
GO:0098978	Component	Glutamatergic synapse	IBA	21873635
GO:0098978	Component	Glutamatergic synapse	IDA	17989287
GO:0098978	Component	Glutamatergic synapse	IMP	17989287
GO:0106027	Process	Neuron projection organization	ISS
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:0150101	Process	Regulation of microtubule anchoring at centrosome	IMP	17139249
GO:1900034	Process	Regulation of cellular response to heat	TAS
GO:1900181	Process	Negative regulation of protein localization to nucleus	ISS
GO:1900271	Process	Regulation of long-term synaptic potentiation	ISS
GO:1901030	Process	Positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	ISS
GO:1901215	Process	Negative regulation of neuron death	IDA	19830702
GO:1901216	Process	Positive regulation of neuron death	IDA	18508033
GO:1901984	Process	Negative regulation of protein acetylation	ISS
GO:1902042	Process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IMP	18846110
GO:1904339	Process	Negative regulation of dopaminergic neuron differentiation	TAS	24431302
GO:1904646	Process	Cellular response to amyloid-beta	ISS
GO:1904781	Process	Positive regulation of protein localization to centrosome	IMP	17139249
GO:1904885	Process	Beta-catenin destruction complex assembly	TAS
GO:1904886	Process	Beta-catenin destruction complex disassembly	TAS
GO:1990909	Component	Wnt signalosome	TAS	24115276
GO:2000077	Process	Negative regulation of type B pancreatic cell development	TAS	19366350
GO:2000300	Process	Regulation of synaptic vesicle exocytosis	EXP	17989287
GO:2000300	Process	Regulation of synaptic vesicle exocytosis	IDA	17989287
GO:2000300	Process	Regulation of synaptic vesicle exocytosis	IMP	17989287
GO:2000466	Process	Negative regulation of glycogen (starch) synthase activity	TAS	19366350

Other IDs

• MIM: 605004
• HGNC: 4617
• e!Ensembl: ENSG00000082701

Protein

• UniProt ID: P49841
• Protein name: Glycogen synthase kinase-3 beta (GSK-3 beta) (EC 2.7.11.26) (Serine/threonine-protein kinase GSK3B) (EC 2.7.11.1)
• Protein function: 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. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. 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 and diabetes. 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 SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. 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:19946213, PubMed:28903391). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression (By similarity). 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:30704899). 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 (PubMed:18846110).
• PDB: 1GNG, 1H8F, 1I09, 1J1B, 1J1C, 1O6K, 1O6L, 1O9U, 1PYX, 1Q3D, 1Q3W, 1Q41, 1Q4L, 1Q5K, 1R0E, 1UV5, 2JDO, 2JDR, 2JLD, 2O5K, 2OW3, 2UW9, 2X39, 2XH5, 3CQU, 3CQW, 3DU8, 3E87, 3E88, 3E8D, 3F7Z, 3F88, 3GB2, 3I4B, 3L1S, 3M1S, 3MV5, 3OW4, 3PUP, 3Q3B, 3QKK, 3SAY, 3SD0, 3ZDI, 3ZRK, 3ZRL, 3ZRM, 4ACC, 4ACD, 4ACG, 4ACH
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	56 → 340	Protein kinase domain	Domain

• Sequence:

  MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTK
  VIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSG
  EKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHR
  DIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDV
  WSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHP
  WTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALF
  NFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST
  

• Sequence length: 420

Pathways

KEGG:

EGFR tyrosine kinase inhibitor resistance
ErbB signaling pathway
Chemokine signaling pathway
Cell cycle
mTOR signaling pathway
PI3K-Akt signaling pathway
Wnt signaling pathway
Hedgehog signaling pathway
Axon guidance
Hippo signaling pathway
Focal adhesion
Signaling pathways regulating pluripotency of stem cells
IL-17 signaling pathway
T cell receptor signaling pathway
B cell receptor signaling pathway
Neurotrophin signaling pathway
Dopaminergic synapse
Insulin signaling pathway
Melanogenesis
Prolactin signaling pathway
Thyroid hormone signaling pathway
Insulin resistance
Non-alcoholic fatty liver disease
Cushing syndrome
Growth hormone synthesis, secretion and action
Alcoholic liver disease
Alzheimer disease
Prion disease
Pathways of neurodegeneration - multiple diseases
Shigellosis
Yersinia infection
Hepatitis C
Measles
Human cytomegalovirus infection
Human papillomavirus infection
Kaposi sarcoma-associated herpesvirus infection
Pathways in cancer
Colorectal cancer
Endometrial cancer
Prostate cancer
Basal cell carcinoma
Breast cancer
Hepatocellular carcinoma
Gastric cancer
Diabetic cardiomyopathy
Lipid and atherosclerosis

Reactome:

Degradation of beta-catenin by the destruction complex
Beta-catenin phosphorylation cascade
Regulation of HSF1-mediated heat shock response
CRMPs in Sema3A signaling
Disassembly of the destruction complex and recruitment of AXIN to the membrane
B-WICH complex positively regulates rRNA expression
Misspliced GSK3beta mutants stabilize beta-catenin
S33 mutants of beta-catenin aren't phosphorylated
S37 mutants of beta-catenin aren't phosphorylated
S45 mutants of beta-catenin aren't phosphorylated
T41 mutants of beta-catenin aren't phosphorylated
APC truncation mutants have impaired AXIN binding
AXIN missense mutants destabilize the destruction complex
Truncations of AMER1 destabilize the destruction complex
GLI3 is processed to GLI3R by the proteasome
Constitutive Signaling by AKT1 E17K in Cancer

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Neuronal ceroid lipofuscinosis	CEROID LIPOFUSCINOSIS, NEURONAL, 6	rs118203975, rs118203976, rs118203977, rs267607235, rs140948465, rs1740291234, rs386833969, rs104894385, rs104894386, rs121908292, rs267606738, rs1555274312, rs119455953, rs119455954, rs119455955, rs56144125, rs119455956, rs28940573, rs119455957, rs119455958, rs104894064, rs28940569, rs104894060, rs137852883, rs1555468634, rs-1, rs121434286, rs267606737, rs104894483, rs397515352, rs774543080, rs121908080, rs786205067, rs137852695, rs137852696, rs137852697, rs137852698, rs137852699, rs137852700, rs137852701, rs137852702, rs63749877, rs121912789, rs121912790, rs786205105, rs154774634, rs587776892, rs387907246, rs386833624, rs386833626, rs386833625, rs386833627, rs386833628, rs386833629, rs386833630, rs386833632, rs386833633, rs386833634, rs386833635, rs386833636, rs386833637, rs386833638, rs386833641, rs386833642, rs386833643, rs386833644, rs386833645, rs386833646, rs386833647, rs386833648, rs386833649, rs386833650, rs386833651, rs386833652, rs386833653, rs148412181, rs386833654, rs386833655, rs386833656, rs386833657, rs386833658, rs386833659, rs386833660, rs386833661, rs386833663, rs386833664, rs386833665, rs386833666, rs386833667, rs386833668, rs386833669, rs386833671, rs386833694, rs386833695, rs386833696, rs386833697, rs386833698, rs386833699, rs386833700, rs386833701, rs386833702, rs386833703, rs386833704, rs386833705, rs386833706, rs386833707, rs386833708, rs386833709, rs386833710, rs386833712, rs386833713, rs386833714, rs386833715, rs386833717, rs386833720, rs386833721, rs386833722, rs386833724, rs386833725, rs386833726, rs386833728, rs386833729, rs386833730, rs386833731, rs386833732, rs386833735, rs386833736, rs386833737, rs386833739, rs386833740, rs386833741, rs386833742, rs386833743, rs386833744, rs386833963, rs386833964, rs386833965, rs386833966, rs386833967, rs386833970, rs386833971, rs386833972, rs386833973, rs386833974, rs386833975, rs386833978, rs386833979, rs386833980, rs386833981, rs386833982, rs386833983, rs386834123, rs386834124, rs386834125, rs386834126, rs386834128, rs386834130, rs386834132, rs386834133, rs386834135, rs34238807, rs386834138, rs386834139, rs397514731, rs397514732, rs753084727, rs587778809, rs154774640, rs154774639, rs121908197, rs121908198, rs121908199, rs121908200, rs121908201, rs121908203, rs121908202, rs121908195, rs121908204, rs121908205, rs121908209, rs121908207, rs104895127, rs63750411, rs587779397, rs587780315, rs724159970, rs727502800, rs727502801, rs724159971, rs746645358, rs786204553, rs786204753, rs778232650, rs786204644, rs794727955, rs794729218, rs796052925, rs796052923, rs796052927, rs558274487, rs796052752, rs144495588, rs1554901472, rs750428882, rs796053439, rs763162812, rs756564767, rs202189057, rs759080581, rs746085696, rs546989392, rs143781303, rs796052356, rs796052351, rs796052335, rs797045136, rs797045137, rs765097897, rs864309505, rs869025274, rs869312751, rs1085307087, rs878853322, rs878853325, rs878853929, rs878855053, rs878855331, rs553522118, rs748710466, rs886041568, rs886041487, rs886041546, rs1057516575, rs1057516889, rs1057517401, rs1057516447, rs1057517049, rs1057517192, rs1057517368, rs1057517112, rs747204624, rs1057516867, rs1057516582, rs756267448, rs1057516579, rs1057516511, rs1057516264, rs1057516319, rs113019349, rs1057517313, rs1057516945, rs752164603, rs1057516366, rs1057516667, rs1057516814, rs780198002, rs1057517134, rs1057516390, rs764495616, rs750935331, rs1057516677, rs1057516267, rs771788391, rs1057517350, rs1057516335, rs1057517287, rs1057517215, rs1057516343, rs777625354, rs764051026, rs559155109, rs1064796787, rs139842473, rs1064794233, rs181995380, rs1064795153, rs752612332, rs1131691676, rs1131691539, rs1555438255, rs1555058286, rs1555274005, rs1555468632, rs200348035, rs1265044710, rs1439582451, rs751696703, rs761621368, rs143730802, rs1554901580, rs1554902052, rs1553950197, rs200319160, rs143657539, rs1554901523, rs1555274338, rs1555273604, rs1555273881, rs1216139602, rs762226836, rs1553167863, rs1553166135, rs1553166147, rs1553167430, rs1349528345, rs1553166499, rs1553166337, rs1553167415, rs1553167474, rs1553167479, rs1554451504, rs746397087, rs1554449028, rs759830733, rs1554449124, rs554042394, rs1554451484, rs1554448874, rs1554448924, rs1554449047, rs1554449136, rs1554901463, rs1184563885, rs1554902043, rs763961289, rs1407106889, rs1554901576, rs1554901731, rs1424116749, rs1554901784, rs1554902216, rs779615685, rs1554902085, rs764790770, rs1555274343, rs1555274369, rs1555273567, rs1555274365, rs1555273609, rs1555274344, rs1555274373, rs1555274387, rs1451777867, rs762902907, rs756522171, rs1555438212, rs1555438443, rs1555468374, rs1555469452, rs1555467473, rs1418997146, rs1555273882, rs1478660606, rs1555273992, rs1555274014, rs1555274337, rs142456044, rs1555469159, rs758921701, rs1555469089, rs1555469477, rs1554901898, rs1554902217, rs1564855860, rs1564854729, rs1460276679, rs1560776422, rs556661896, rs868732642, rs1564855725, rs1566219136, rs1381427322, rs1557714302, rs1593914689, rs1302326945, rs1570470281, rs1570476221, rs775699005, rs1578912362, rs750162094, rs759664259, rs1589947644, rs1012449574, rs1570467252, rs778875017, rs1578794927, rs1578912759, rs1314967038, rs1465284719, rs1595816465, rs1595816474, rs1596563048, rs1565311875, rs2046113301, rs1578889355, rs776253867, rs1649597261, rs1649901192, rs749315686, rs1801297484, rs764256845, rs1242337070, rs2034349431, rs1380684360, rs1648444864, rs1739594685, rs1736369601, rs1739482158, rs1471253353, rs2046243804, rs1845791308, rs1397197980, rs2046158549	23516525
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs-1, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	31563592, 14745448
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	16421604, 25246272
Myocardial infarction	Myocardial Infarction, Myocardial Failure	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	16716347, 17901358
Alzheimer disease	Familial Alzheimer Disease (FAD), Alzheimer Disease, Late Onset, Alzheimer Disease, Early Onset, Alzheimer`s Disease, Alzheimer`s Disease, Focal Onset	rs63750215, rs28936379, rs63749851, rs63749884, rs28936380, rs63750048, rs63750579, rs63750264, rs63749964, rs63750671, rs281865161, rs63750066, rs63750399, rs63750734, rs63751039, rs63750973, rs63749810, rs63750643, rs-1, rs193922916, rs63750306, rs63750590, rs63750526, rs63751235, rs661, rs63751037, rs63749885, rs63750231, rs63751229, rs63751272, rs63751223, rs63750391, rs63751163, rs281875357, rs63751141, rs63750082, rs121917807, rs63751399, rs63750265, rs63751144, rs63750886, rs63751068, rs121917808, rs63749891, rs63750083, rs63749824, rs63750577, rs267606983, rs63750218, rs63751287, rs63750900, rs145518263, rs63751475, rs63750450, rs63749805, rs63751278, rs63751106, rs63750004, rs63749806, rs63751024, rs63750248, rs63750779, rs63751139, rs63750219, rs63750298, rs63750687, rs63750851, rs1553268799, rs1561901881, rs1561905293, rs866101707, rs1566638673, rs63750009, rs1566656702, rs1566657804, rs1567885728, rs1568339995, rs1566630791, rs1555358260, rs63750964, rs1594998354, rs63751316	22944069, 17409235, 29274321
Hypertension	Hypertensive disease	rs13306026	22982863
Multiple congenital anomalies	Multiple congenital anomalies	rs-1, rs1057517732	22975441

Unknown
Disease name	Disease term	dbSNP ID	References
Heart failure	Heart failure, Left-Sided Heart Failure, Heart Failure, Right-Sided	rs121918074, rs142027794, rs148791216, rs72648927, rs71578935, rs142416150, rs199830512, rs755445214, rs150102469, rs779568205, rs907992794, rs1202130741	17901358
Congestive heart failure	Congestive heart failure	rs2301610, rs3833910, rs12301951, rs201674674, rs186741807, rs150140412, rs786205727, rs757840030, rs552050895, rs759465783, rs201978086, rs572757800, rs1572143354, rs749160569	17901358
Mental depression	Mental Depression, Endogenous depression, Depressive disorder, Unipolar Depression, Depressive Syndrome, Depression, Neurotic, Major Depressive Disorder	rs587778876, rs587778877	23188793, 21315744, 17628506, 20534517, 20357757, 24677591, 24927694, 20618448, 24001941, 23030648
Bipolar disorder	Bipolar Disorder, Depression, Bipolar		24677591, 23440732, 24929537, 24992082, 20357757, 22990942
Cognitive disorder	Cognition Disorders		24634145
Kidney failure	Kidney Failure, Acute		22785175
Malignant lymphoma, lymphocytic, intermediate differentiation	Malignant lymphoma, lymphocytic, intermediate differentiation, diffuse		18787224
Lymphoma, lymphocytic, intermediate	Lymphoma, Lymphocytic, Intermediate		18787224
Manic disorder	Manic, Manic Disorder		20357757
Melancholia	Melancholia		20357757, 20534517
Mood disorder	Mood Disorders		20618448, 20219685
Peritonitis	Primary Peritonitis, Secondary Peritonitis		16713974
Prostatic neoplasms	Prostatic Neoplasms		25246272, 16421604
Acute kidney insufficiency	Acute Kidney Insufficiency		22785175
Senile dementia	Presenile dementia, Acute Confusional Senile Dementia		17409235, 22944069
Tauopathies	Tauopathies		26945731