GSK3B and HDAC4

Data Source:
BioGRID (enzymatic study)

		GSK3B	HDAC4
Description		glycogen synthase kinase 3 beta	histone deacetylase 4
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GO Annotations	Cellular Component	Nucleus Nucleoplasm Cytoplasm Mitochondrion Centrosome Cytosol Plasma Membrane Axon Dendrite Beta-catenin Destruction Complex Postsynapse Glutamatergic Synapse Wnt Signalosome	Histone Deacetylase Complex Nucleus Nucleoplasm Cytoplasm Cytosol Nuclear Speck Transcription Repressor Complex Z Disc Neuromuscular Junction A Band Actomyosin
	Molecular Function	RNA Polymerase II Transcription Factor Binding Protease Binding P53 Binding Protein Kinase Activity Protein Serine/threonine Kinase Activity Protein Binding ATP Binding Beta-catenin Binding Kinase Activity Protein Kinase Binding Ubiquitin Protein Ligase Binding Protein Kinase A Catalytic Subunit Binding Dynactin Binding Tau Protein Binding Tau-protein Kinase Activity NF-kappaB Binding Protein Serine Kinase Activity Protein Threonine Kinase Activity	Transcription Regulatory Region Sequence-specific DNA Binding RNA Polymerase II Cis-regulatory Region Sequence-specific DNA Binding RNA Polymerase II Transcription Factor Binding Transcription Corepressor Activity Histone Deacetylase Activity Protein Binding Transcription Factor Binding Zinc Ion Binding SUMO Transferase Activity Protein Kinase Binding Potassium Ion Binding NAD-dependent Histone Deacetylase Activity (H3-K14 Specific) Protein Deacetylase Activity Activating Transcription Factor Binding Identical Protein Binding Histone Deacetylase Binding Sequence-specific DNA Binding Repressing Transcription Factor Binding Promoter-specific Chromatin Binding
	Biological Process	Epithelial To Mesenchymal Transition Positive Regulation Of Cell-matrix Adhesion Glycogen Metabolic Process Protein Phosphorylation ER Overload Response Signal Transduction Dopamine Receptor Signaling Pathway Circadian Rhythm Insulin Receptor Signaling Pathway Positive Regulation Of Autophagy Positive Regulation Of Gene Expression Positive Regulation Of Mitochondrion Organization Regulation Of Neuron Projection Development Wnt Signaling Pathway Peptidyl-serine Phosphorylation Peptidyl-threonine Phosphorylation Hippocampus Development Establishment Of Cell Polarity Maintenance Of Cell Polarity Regulation Of Axon Extension Neuron Projection Development Negative Regulation Of Protein-containing Complex Assembly Positive Regulation Of Protein-containing Complex Assembly Negative Regulation Of Protein Binding Positive Regulation Of Protein Binding Positive Regulation Of Proteasomal Ubiquitin-dependent Protein Catabolic Process Negative Regulation Of Phosphoprotein Phosphatase Activity Regulation Of Microtubule-based Process Intracellular Signal Transduction Cellular Response To Interleukin-3 Regulation Of Circadian Rhythm Negative Regulation Of Apoptotic Process Positive Regulation Of GTPase Activity Negative Regulation Of Glycogen Biosynthetic Process Positive Regulation Of Protein Catabolic Process Protein Autophosphorylation Positive Regulation Of Protein Export From Nucleus Regulation Of Dendrite Morphogenesis Regulation Of Axonogenesis Excitatory Postsynaptic Potential Regulation Of Microtubule Cytoskeleton Organization Negative Regulation Of Calcineurin-NFAT Signaling Cascade Superior Temporal Gyrus Development Negative Regulation Of Canonical Wnt Signaling Pathway Extrinsic Apoptotic Signaling Pathway Extrinsic Apoptotic Signaling Pathway In Absence Of Ligand Neuron Projection Organization Regulation Of Microtubule Anchoring At Centrosome Regulation Of Cellular Response To Heat Negative Regulation Of Protein Localization To Nucleus Regulation Of Long-term Synaptic Potentiation Positive Regulation Of Mitochondrial Outer Membrane Permeabilization Involved In Apoptotic Signaling Pathway Negative Regulation Of Neuron Death Positive Regulation Of Neuron Death Negative Regulation Of Protein Acetylation Negative Regulation Of Extrinsic Apoptotic Signaling Pathway Via Death Domain Receptors Negative Regulation Of Dopaminergic Neuron Differentiation Cellular Response To Amyloid-beta Positive Regulation Of Protein Localization To Centrosome Beta-catenin Destruction Complex Assembly Beta-catenin Destruction Complex Disassembly Negative Regulation Of Type B Pancreatic Cell Development Regulation Of Synaptic Vesicle Exocytosis Negative Regulation Of Glycogen (starch) Synthase Activity	Negative Regulation Of Transcription By RNA Polymerase II Skeletal System Development Osteoblast Development Chromatin Remodeling Protein Deacetylation Inflammatory Response Nervous System Development Positive Regulation Of Cell Population Proliferation Negative Regulation Of Cell Population Proliferation Positive Regulation Of Lamellipodium Assembly Negative Regulation Of Myotube Differentiation Regulation Of Cardiac Muscle Contraction By Calcium Ion Signaling Response To Denervation Involved In Regulation Of Muscle Adaptation Cardiac Muscle Hypertrophy In Response To Stress Positive Regulation Of Smooth Muscle Cell Migration Histone Deacetylation Protein Sumoylation B Cell Differentiation Positive Regulation Of Protein Sumoylation Peptidyl-lysine Deacetylation Regulation Of Gene Expression, Epigenetic B Cell Activation Response To Drug Regulation Of Protein Binding Negative Regulation Of DNA-binding Transcription Factor Activity Positive Regulation Of Neuron Apoptotic Process Negative Regulation Of Osteoblast Differentiation Negative Regulation Of Glycolytic Process Negative Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription By RNA Polymerase II Positive Regulation Of Smooth Muscle Cell Proliferation Regulation Of Skeletal Muscle Fiber Development Positive Regulation Of DNA-binding Transcription Factor Activity Response To Interleukin-1 Histone H3 Deacetylation Histone H4 Deacetylation Cellular Response To Mechanical Stimulus Cellular Response To Tumor Necrosis Factor Cellular Response To Parathyroid Hormone Stimulus Positive Regulation Of Male Mating Behavior Negative Regulation Of Pri-miRNA Transcription By RNA Polymerase II Positive Regulation Of Reactive Oxygen Species Biosynthetic Process
Pathways		Degradation of beta-catenin by the destruction complex Beta-catenin phosphorylation cascade AKT phosphorylates targets in the cytosol Regulation of HSF1-mediated heat shock response CRMPs in Sema3A signaling Disassembly of the destruction complex and recruitment of AXIN to the membrane Disassembly of the destruction complex and recruitment of AXIN to the membrane B-WICH complex positively regulates rRNA expression Signaling by GSK3beta mutants 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 Degradation of GLI2 by the proteasome GLI3 is processed to GLI3R by the proteasome Constitutive Signaling by AKT1 E17K in Cancer Ubiquitin-dependent degradation of Cyclin D Regulation of RUNX2 expression and activity Replication of the SARS-CoV-1 genome Maturation of nucleoprotein Maturation of nucleoprotein Maturation of nucleoprotein Replication of the SARS-CoV-2 genome	NOTCH1 Intracellular Domain Regulates Transcription Constitutive Signaling by NOTCH1 PEST Domain Mutants Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants Notch-HLH transcription pathway SUMOylation of intracellular receptors SUMOylation of chromatin organization proteins RUNX2 regulates chondrocyte maturation RUNX3 regulates p14-ARF
Drugs		Lithium cation 3-[3-(2,3-Dihydroxy-Propylamino)-Phenyl]-4-(5-Fluoro-1-Methyl-1h-Indol-3-Yl)-Pyrrole-2,5-Dione SB-409513 AR-AO-14418 Staurosporine Indirubin-3'-monoxime 6-bromoindirubin-3'-oxime Alsterpaullone Phosphoaminophosphonic Acid-Adenylate Ester 2-(1,3-benzodioxol-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazole 5-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazole-2(3H)-thione (7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine 3-({[(3S)-3,4-dihydroxybutyl]oxy}amino)-1H,2'H-2,3'-biindol-2'-one N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE Fostamatinib Tideglusib Lithium citrate Lithium succinate Lithium carbonate	Zinc Belinostat Romidepsin Panobinostat N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamide 2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL Zinc acetate Zinc chloride Zinc sulfate, unspecified form
Diseases			Brachydacytly-mental retardation syndrome and Smith-Magenis syndrome
GWAS		HDL cholesterol ( 24097068) HDL cholesterol levels ( 28334899) Hippocampal volume in Alzheimer's disease dementia ( 29274321) Low density lipoprotein cholesterol levels ( 32154731) Neutrophil count ( 32888494) Platelet distribution width ( 32888494)	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL) ( 28090653) Amyotrophic lateral sclerosis in C9orf72 mutation positive individuals ( 22959728) Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined) ( 23453885) Blond vs. brown/black hair color ( 30531825) Body size at age 10 ( 32376654) Chronotype ( 30696823) CV-A6-associated hand, foot, and mouth disease (severe vs mild) ( 32634583) Diastolic blood pressure ( 30224653 30487518) Estimated glomerular filtration rate after 5 years in renal transplantation (recipient effect) ( 30920136) Heel bone mineral density ( 30598549) Intra-individual response time variability (selective attention) ( 30287865) Male-pattern baldness ( 22693459) Mean arterial pressure ( 29403010 30487518) Nevus count ( 30429480) Nevus count or cutaneous melanoma ( 30429480) Obstructive sleep apnea trait (apnea hypopnea index) ( 29077507) Perioperative myocardial infarction in coronary artery bypass surgery ( 25948407) Pulmonary function ( 21946350) Pulmonary function (smoking interaction) ( 23284291) Systolic blood pressure ( 30487518)
Interacting Genes		225 interacting genes: ACLY ACSBG1 ACTL6B ADAP1 ADIRF AKAP11 AKT1 AKT2 AKT3 APC APP AR ARRB1 ASRGL1 ATP5IF1 ATXN3 AURKA AXIN1 AXIN2 BAG6 BCL2A1 BCL2L1 BCL3 BEX1 BHLHE41 BICD1 BICD2 BRIX1 BTRC BZW2 CABYR CAMSAP3 CCND1 CCNE1 CDH1 CDK5 CDX2 CEBPA CEBPD CEBPZ CENPB CHD3 CIITA CLEC3B CREB1 CREB3L3 CREM CSAD CSNK2B CST6 CTNNB1 CTNND1 DBI DCTN1 DCTN2 DCTN3 DDIT4 DEAF1 DEFA1 DELEC1 DHX34 DISC1 DNAJC13 DNM1L DNMT1 DNMT3L DPYSL2 DUSP9 DYNC1I1 E2F1 EEF1G EFTUD2 EIF2B5 EIF4EBP1 ENTPD6 ERG28 EYA1 FAM193B FAM83D FBN3 FBXO7 FBXW11 FEN1 FIBP FKBP14 FOXO1 FRAT1 FRAT2 FZD5 GBP2 GFI1 GIPC1 GJB5 GNB2 GPR39 GYS1 HDAC4 HNRNPD HSP90AA1 HSPA4 IGHM IGSF21 IKBKG ILK IQCG IRF1 JUN KDM1A KHSRP KIAA1191 KIF5B KLF2 KLF5 LMO4 LPCAT1 LRP6 LUC7L2 MAP1B MAP3K1 MAP3K4 MAP4 MAPK1 MAPT MARK2 MASP1 MCL1 MDM2 MED24 MICAL1 MID1IP1 MITF MPP1 MTF2 MTOR MUC1 MYC MYOCD NAT9 NBR1 NCOA3 NDRG1 NFE2L1 NFE2L2 NFE2L3 NFKB1 NIN NOTCH1 NOTCH2 NRBP1 NSFL1C OGA OGT PDE4D PFKFB4 PHLPP1 PIAS1 PIM2 PMAIP1 PPARGC1A PPP1R2 PRKACA PRKCA PRKCB PRKCZ PRKDC PSEN1 PTK2 PTN PTPN1 PXN QARS1 RAI1 RBPJ RCAN1 RELB RICTOR RPL36AL RPLP1 RPS2 RPS6KA1 RSU1 RXRA SAP30BP SGK1 SGK3 SLA SMAD3 SNAI1 SNCA SNCAIP SOX10 SPTBN4 SREBF1 STAT2 SYNE4 TAZ TLE1 TMEM132A TMEM44 TNFAIP3 TONSL TP53 TPPP TRAF6 TSC2 TUBA1A UBE2D1 UBR1 UBR5 UBXN6 UFM1 UPF3A VIM VPS51 WSB1 XIAP XPNPEP1 YBX1 YBX3 YWHAZ ZFPM1 ZHX1 ZNF135 ZNF227 ZNF746	123 interacting genes: ACTA1 ANKRA2 ANKRD11 APP AR ASB15 ATF3 ATRX BCL6 BCOR BEGAIN BICD2 BLZF1 BORCS8-MEF2B BRMS1 CACNA1C CADPS CALCOCO2 CAMK4 CBX5 CCDC125 CCDC136 CCNDBP1 CDKN1A CDPF1 CDR2 CDR2L CEBPD CEP70 CIITA CSRP3 CTBP1 DYDC1 EFEMP2 EFHC2 ESR1 FCHSD2 FSD2 GATA1 GCM1 GOLGA2 GOLGA6L9 GRIPAP1 GSK3B HAP1 HDAC3 HDAC7 HDAC9 HNF4A HOOK2 HSF2BP IFRD1 IKZF2 INCA1 JDP2 KRT27 KRT31 KRT33B KRT34 KRT35 KRT38 KRT40 LCOR LDOC1 LZTR1 MAP1S MAPK1 MAPK3 MECOM MEF2A MEF2B MEF2C MEF2D MEGF10 MID2 MIF4GD MTUS2 NACC1 NCOR2 NFKB2 NFKBID NFKBIE NPPB NR1H2 NR2C1 NR2C2 PICK1 PNMA1 PPARD PPARG PTPA RANBP2 RARA RBBP4 REV3L RFXANK RINT1 RUNX2 RUNX3 RUVBL2 RXRA SMAD3 SRF SS18L1 SSX2IP SUMO1 SUMO2 SYK TFIP11 TLE5 TNFRSF14 TRIB3 TRIM27 TSGA10 UBE2I VPS52 YWHAE YWHAG YWHAQ YWHAZ ZBTB16 ZMYND12 ZNF354A
Entrez ID		2932	9759
HPRD ID		05418	05610
Ensembl ID		ENSG00000082701	ENSG00000068024
Uniprot IDs		P49841 Q6FI27	P56524
PDB IDs		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 4AFJ 4B7T 4DIT 4EKK 4IQ6 4J1R 4J71 4NM0 4NM3 4NM5 4NM7 4PTC 4PTE 4PTG 5F94 5F95 5HLN 5HLP 5K5N 5KPK 5KPL 5KPM 5OY4 5T31 6B8J 6BUU 6GJO 6GN1 6H0U 6HK3 6HK4 6HK7 6NPZ 6TCU 6V6L 6Y9R 6Y9S	2H8N 2O94 2VQJ 2VQM 2VQO 2VQQ 2VQV 2VQW 3UXG 3UZD 3V31 4CBT 4CBY 5A2S 5ZOO 5ZOP 6FYZ
Enriched GO Terms of Interacting Partners?
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