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Symbol SGK1 contributors: mct/npt/pgu - updated : 04-11-2016
HGNC name serum/glucocorticoid regulated kinase 1
HGNC id 10810
Location 6q23.2      Physical location : 134.490.384 - 134.639.196
Synonym name
  • serine/threonine protein kinase SGK1
  • Serum/glucocorticoid-regulated kinase
  • Synonym symbol(s) SGK
    EC.number, 2.7.1.-
    TYPE functioning gene
    STRUCTURE 148.81 kb     12 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map cen - D6S472 - SGK1 - D6S553 - qter
    Authors Gene Map (99)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 2414 48 431 - 1999 10548550
    14 - 3208 - 526 - 1999 10548550
    12 - 2459 - 459 - 1999 10548550
    12 - 2638 - 445 - 1999 10548550
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
     mouth   highly
    Endocrineadrenal gland   highly
     pancreas   highly
     parathyroid   highly
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • from the N terminus, the usual nine motifs of STKs motif 1 highly conserved sequence GXGXXG
  • motif 7 containing the conserved sequence, Asp-Phe-Gly both involved in ATP binding
  • motif 8 has a key sequence of the highly conserved catalytic structure Ala-Pro-Glu
    interspecies ortholog to murine Sgk
    intraspecies homolog to PKB ( 60 p100 )
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • playing an important role in cellular stress response
  • may be involved in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion
  • capable to regulate the cell surface expression of several metabolite transporters including the insulin-sensitive facilitative glucose transporter SLC2A1
  • may contributing to the stimulation of cellular glucose uptake by insulin
  • stimulating glucose transport by enhancing the abundance of the facilitative glucose transporter SLC2A4 in the cell membrane at least in part via direct SLC2A4 phosphorylation
  • playing a key role in the molecular pathway of cell death, in which SGK1 seems to exert a protective role
  • having capacity to modulate expression of ion channels and transporters at the plasma membrane of many cell types also providing a means to alter membrane excitability in neurons
  • having multiple functions as a modulator of neuronal plasticity and a mediator of neuronal survival
  • also important in transduction of growth factors and steroid-dependent survival signals and may have a role in the development of resistance to cancer chemotherapy
  • participates in the stimulation of renal tubular glucose transport in diabetes, the renal profibrotic effect of both angiotensin II and aldosterone, and in fetal programing of arterial hypertension
  • involved in the regulation of epithelial transport through phosphorylation of the ubiquitin protein ligase NEDD4L
  • SGK1/SGK3 are novel potent stimulators of SLC6A19 and may thus participate in the regulation of neutral amino acid transport
  • short-lived protein, predominantly targeted to the endoplasmic reticulum (ER) to undergo rapid proteasome-mediated degradation through the ER-associated degradation (ERAD) system
  • inhibits the NOTCH1 signaling pathway via phosphorylation of FBXW7
  • highly cytokine-responsive gene in myeloma cells promoting their malignant growth
  • its regulation is important for ensuring uterine receptivity and maintenance of pregnancy
  • activation of platelets by thrombin leads to up-regulation of SGK1 and ORAI1 protein expression, an effect expected to further enhance activation-dependent Ca2+ entry into platelets with subsequent Ca2+-dependent degranulation, adhesion, aggregation and thrombus formation
  • is a positive regulator of constitutive albumin uptake in renal proximal tubule cells
  • neuronal expression of SGK1 in aged human brain and its nuclear compartmentalization suggest a possible neuroprotective role
  • is a mediator for the effects of cortisol on neurogenesis and glucocorticoid receptor (GR) function, with particular relevance to stress and depression
  • likely plays a key role in regulating neutrophil survival signaling
  • is important to the regulation of macrophage activation that contributes to the development of pulmonary arterial hypertension (PAH)
  • growth factor-responsive kinase, having a molecular role in stimulation of VSMC proliferation
  • role for SGK1 in stimulation of arterial VSMC growth via regulation of CTNNB1 dynamics and SGK1 is implicated in the progression of intimal narrowing following arterial injury
  • SGK1 and NDRG1 participate in the regulation of NFKB1 signaling and maturation of dendritic cells (DCs)
  • roles of AKT1 and SGK1 in the regulation of renal tubular transport
    PI3K signaling cascade
    a component
    small molecule
  • interacts with NEDD4 and NEDD4L
  • regulating SLC5A1
  • regulating BSND and participating in the regulation of transport in kidney and inner ear
  • regulating the glucose transporter GLUT4 (SLC2A4)
  • interacting with SGK3 and SLC6A8 (increase SLC6A8 activity by increasing the maximal transport rate of the carrier)
  • target of SGK1 is the epithelial sodium channel, SCNN1A, SCNN1B, SCNN1C, SCNN1G, which plays a crucial role in the regulation of body sodium
  • SGK1, SGK2, SGK3 participate in the regulation of KCNE1-dependent transport and excitability
  • interacting with TP53 (down-regulates the expression of TP53 by enhancing its mono- and polyubiquitylation)
  • target of the glucocorticoid receptor (GR) and is central to the stress response in many human tissues
  • TSC22D3 and SGK1
  • is a powerful stimulator of ORAI1 protein abundance
  • SGK1, SGK2, SGK3 are novel potent stimulators of SLC6A19 and may thus participate in the regulation of neutral amino acid transport
  • synergize to markedly stimulate SCNN1A surface expression, by antagonizing the effects of the inhibitory components)
  • is essential for hormonal regulation of SCNN1A-mediated sodium transport and is involved in the transduction of growth-factor-dependent cell survival and proliferation
  • specific interaction between SGK1 and ASPG
  • MAPKAP1 mediates SGK1 protein interaction with CRTC2 protein complex and is required for selective activation of the epithelial sodium channel
  • thrombin decreases SGK1 mRNA and enhances SGK1 protein
  • CNKSR3 physically interacts with SCNN1A, B, D, NEDD4L, and SGK1 and stimulates SCNN1A, SCNN1B, SCNN1D function in a PDZ domain-dependent, aldosterone-induced manner
  • enhances the expression level of mature KCNH2 channels by inhibiting NEDD4L as well as by promoting RAB11-mediated KCNH2 recycling (PMMID: 23589291)
  • specific role of ASPG as an interacting partner of the serum- and glucocorticoid-induced serine/threonine protein kinase SGK1, an enzyme involved in various cell proliferation pathways
  • SGK1 phosphorylates SHANK2 as well as a peptide containing the first SGK1 consensus motif of SHANK2
  • glucocorticoid-induced increase in CFTR abundance requires phosphorylation of SHANK2 at an SGK1 consensus site
  • SGK1-induced hypertrophy of cardiomyocytes involves CDKN1B phosphorylation at T197, which fosters cytoplasmic CDKN1B localization
  • regulation of GRIK2 by SGK1 and NDRG2 in astrocytes may play an important role in gliotransmission, modulation of gene expression and regulation of exocytosis of tissue-type plasminogen activator (tPA)
  • MTA1 is a novel corepressor of serum and glucocorticoid-inducible kinase 1 (SGK1)
  • cell & other
    activated by PDPK1
    serum, steroids, insulin, vasopressin, and interleukin 2 at the transcriptional and post-translational levels
    induced by serum or dexamethasone
    inhibited by SRC (SRC inhibits SGK1-mediated phosphorylation hereby restoring the WNK4-mediated inhibition of ROMK channels thus suppressing K secretion)
    Other serum/glucocorticoid regulated
    strongly altered during anisotonic and isotonic cell volume changes
    RICTOR, but not Raptor or MTOR alone, promotes SGK1 ubiquitination
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in clear cell renal carcinoma with good outcome
    constitutional       gain of function
    leading to hypertension but also to enhanced SLC5A1 activity and obesity
    constitutional     --over  
    strongly correlates with the occurrence of cell death
    tumoral somatic mutation      
    in germinal centre B-cell
    constitutional       gain of function
    in Alzheimer disease (AD)
    constitutional       loss of function
    SGK1 deficiency impaired platelet tethering, adhesion and thrombus formation
  • to blood pressure change over time and strength of the insulin-diastolic blood pressure relationship
  • to type 2 diabetes
  • Variant & Polymorphism other
  • polymorphisms increasing the risk of blood pressure change over time and strength of the insulin-diastolic blood pressure relationship
  • risk haplotype (I6CC/E8CC/CT) was significantly more frequent in diabetic patients
  • Candidate gene
    Therapy target
    inhibition of SGK1 activity is a novel therapeutic approach for the treatment of occlusive vascular diseases
    may be a potential therapeutic target for the treatment of pulmonary arterial hypertension
    therapeutic target for the treatment of inflammatory disease