Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT301T1U)

DOT Name Serine/threonine-protein kinase Sgk1 (SGK1)
Synonyms EC 2.7.11.1; Serum/glucocorticoid-regulated kinase 1
Gene Name SGK1
UniProt ID
SGK1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2R5T; 3HDM; 3HDN; 7PUE
EC Number
2.7.11.1
Pfam ID
PF00069 ; PF00433
Sequence
MTVKTEAAKGTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIANNSYACKHPEVQSILKI
SQPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAE
EVFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYIN
GGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTD
FGLCKENIEHNSTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSR
NTAEMYDNILNKPLQLKPNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHVFFSLINW
DDLINKKITPPFNPNVSGPNDLRHFDPEFTEEPVPNSIGKSPDSVLVTASVKEAAEAFLG
FSYAPPTDSFL
Function
Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1.
Tissue Specificity
Expressed in most tissues with highest levels in the pancreas, followed by placenta, kidney and lung. Isoform 2 is strongly expressed in brain and pancreas, weaker in heart, placenta, lung, liver and skeletal muscle.
KEGG Pathway
FoxO sig.ling pathway (hsa04068 )
Efferocytosis (hsa04148 )
mTOR sig.ling pathway (hsa04150 )
PI3K-Akt sig.ling pathway (hsa04151 )
Parathyroid hormone synthesis, secretion and action (hsa04928 )
Aldosterone-regulated sodium reabsorption (hsa04960 )
Reactome Pathway
Stimuli-sensing channels (R-HSA-2672351 )
Regulation of TP53 Degradation (R-HSA-6804757 )
Transcriptional Regulation by MECP2 (R-HSA-8986944 )
NGF-stimulated transcription (R-HSA-9031628 )
PIP3 activates AKT signaling (R-HSA-1257604 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
58 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [4]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [2]
Ivermectin DMDBX5F Approved Ivermectin increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [6]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [7]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [8]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [11]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [12]
Marinol DM70IK5 Approved Marinol decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [13]
Progesterone DMUY35B Approved Progesterone increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [14]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [15]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [16]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [17]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [18]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [15]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [19]
Irinotecan DMP6SC2 Approved Irinotecan increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [20]
Mitomycin DMH0ZJE Approved Mitomycin decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [21]
Melphalan DMOLNHF Approved Melphalan increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [22]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [23]
Pioglitazone DMKJ485 Approved Pioglitazone decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [24]
Acocantherin DM7JT24 Approved Acocantherin decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [25]
Lindane DMB8CNL Approved Lindane increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [23]
Colchicine DM2POTE Approved Colchicine decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [21]
Hydroxyurea DMOQVU9 Approved Hydroxyurea increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [26]
Estrone DM5T6US Approved Estrone increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [15]
Adenine DMZLHKJ Approved Adenine decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [21]
Mestranol DMG3F94 Approved Mestranol increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [15]
Spironolactone DM2AQ5N Approved Spironolactone increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
Norethindrone DMTY169 Approved Norethindrone increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
Cyproterone DMQXLD2 Approved Cyproterone increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [27]
Pregnenolone DM6VFO1 Phase 4 Pregnenolone increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [28]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [29]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [23]
HEXESTROL DM9AGWQ Withdrawn from market HEXESTROL increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [15]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [30]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [32]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [33]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [34]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [35]
chloropicrin DMSGBQA Investigative chloropicrin increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [36]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [23]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [37]
Chlorpyrifos DMKPUI6 Investigative Chlorpyrifos increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [38]
Chrysin DM7V2LG Investigative Chrysin increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
OXYBENZONE DMMZYX6 Investigative OXYBENZONE increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
Daidzein DMRFTJX Investigative Daidzein increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One DMDN12L Investigative 2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One decreases the activity of Serine/threonine-protein kinase Sgk1 (SGK1). [39]
H-89 DM4RVGO Investigative H-89 decreases the activity of Serine/threonine-protein kinase Sgk1 (SGK1). [40]
Indirubin-3'-monoxime DMLRQH0 Investigative Indirubin-3'-monoxime decreases the activity of Serine/threonine-protein kinase Sgk1 (SGK1). [39]
ETHISTERONE DMDXRP1 Investigative ETHISTERONE increases the expression of Serine/threonine-protein kinase Sgk1 (SGK1). [5]
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⏷ Show the Full List of 58 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Serine/threonine-protein kinase Sgk1 (SGK1). [31]
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