SGK3 (SGKL)

SGK3 is serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. SGK3 up-regulates Na+ channels: SCNN1A/ENAC and SCN5A, K+ channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca2+ channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na+/dicarboxylate cotransporter: SLC13A2/NADC1, Na+-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na+/H+ exchanger: SLC9A3/NHE3, and the Na+/K+ ATPase. SGK3 plays a role in the regulation of renal tubular phosphate transport and bone density. SGK3 phosphorylates NEDD4L and GSK3B. SGK3 positively regulates ER transcription activity through phosphorylation of FLII. SGK3 negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.

SGK3 (SGKL) Related Areas

Enzyme>>Protein Kinase>>Intracellular Kinase>>SGK3/SGKL

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>SGK3/SGKL

SGK3 (SGKL) Alternative Names

SGK3, SGKL, CISK, DKFZp781N0293, SGK2 [Homo sapiens]

Sgk3, SGKL, 2510015P22Rik, A330005P07Rik, Cisk, fy, fz [Mus musculus]

Summaries for SGK3 (SGKL)

Entrez Gene summary for SGK3 (SGKL):

SGK3 gene is a member of the Ser/Thr protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The protein phosphorylates several target proteins and has a role in neutral amino acid transport and activation of potassium and chloride channels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Wikipedia summary for SGK3 (SGKL):

Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the SGK3 gene.
This gene is a member of the Ser/Thr protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The protein phosphorylates several target proteins and has a role in neutral amino acid transport and activation of potassium and chloride channels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. In melanocytic cells SGK3 gene expression may be regulated by MITF.

Human SGK3 (SGKL) Protein General Information

 

• Protein names: Serum/glucocorticoid-regulated kinase 3
  Short name=SGK3
• Sequence length: 496 AA.
• Catalytic activity: ATP + a protein = ADP + a phosphoprotein.
• Sequence similarities: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
  Contains 1 AGC-kinase C-terminal domain.
  Contains 1 protein kinase domain.
  Contains 1 PX (phox homology) domain.
• Post-translational modification: Activated by phosphorylation on Ser-486 by an unknown kinase (may be mTORC2 but not confirmed), transforming it into a substrate for PDPK1 which then phosphorylates it on Thr-320.
• Subunit structure: Interacts with GSK3B and FLII. Interacts with PDPK1 in a phosphorylation-dependent manner.
• Subcellular location: Cytoplasmic vesicle . Early endosome. Recycling endosome. Note: Endosomal localization is a prerequisite for complete kinase activity. It is essential for its co-localization with the kinase responsible for phosphorylating Ser-486 thus allowing PDPK1 phosphorylation of Thr-320 resulting in complete activation of SGK3. Localized in vesicle-like structures and in the early endosome. Co-localizes with SLC9A3/NHE3 in the recycling endosomes.
• Tissue specificity: Expressed in most tissues with highest levels in pancreas, kidney liver, heart and brain and lower levels in lung, placenta and skeletal muscle. Expression is higher in ER-positive breast tumors than ER-negative breast tumors.
• Enzyme regulation: Two specific sites, one in the kinase domain (Thr-320) and the other in the C-terminal regulatory region (Ser-486), need to be phosphorylated for its full activation.
• Induction: Induced by estrogen/ER in breast cancer cells.
• Sequence caution: The sequence AAF12758.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

General information above from UniProt

Function for SGK3 (SGKL) Protein

UniProtKB:

SGK3 is serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. SGK3 up-regulates Na⁺ channels: SCNN1A/ENAC and SCN5A, K⁺ channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca²⁺ channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na⁺/dicarboxylate cotransporter: SLC13A2/NADC1, Na⁺-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na⁺/H⁺ exchanger: SLC9A3/NHE3, and the Na⁺/K⁺ ATPase. SGK3 plays a role in the regulation of renal tubular phosphate transport and bone density. SGK3 phosphorylates NEDD4L and GSK3B. SGK3 positively regulates ER transcription activity through phosphorylation of FLII. SGK3 negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.

Genatlas:

• SGK3 plays an important role in activating certain potassium, sodium, and chloride channels
• SGK3 may be involved in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion

Homology for human SGK3 (SGKL)

• ortholog to murine Sgk3
• homolog to SGK1