SGK3 Recombinant Protein

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. [provided by RefSeq, Jul 2008]

Function: 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. 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. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.

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.

Subunit structure: Interacts with GSK3B and FLII. Interacts with PDPK1 in a phosphorylation-dependent manner. Ref.7 Ref.17 Ref.24 Ref.27

Subcellular location: Cytoplasmic vesicle

By similarity. Early endosome. Recycling endosome. Note: Endosomal localization is a prerequisite for complete kinase activity. It is essential for its colocalization 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. Colocalizes with SLC9A3/NHE3 in the recycling endosomes. Ref.24 Ref.29

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. Ref.30

Induction: Induced by estrogen/ER in breast cancer cells. Ref.30

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.

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.

Sequence caution: The sequence AAF12758.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.