SGK3

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 Ca(2+) 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.

Post-translational modifications

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.

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.

Cellular localization

• Cytoplasmic vesicle
• Early endosome
• Recycling endosome
• 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.

Alternative names

CISK, SGKL, SGK3, Serine/threonine-protein kinase Sgk3, Cytokine-independent survival kinase, Serum/glucocorticoid-regulated kinase 3, Serum/glucocorticoid-regulated kinase-like

Database links

swissprot:Q96BR1 omim:607591 entrezGene:23678 entrezGene:100533105