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MGP007305

UniProt Annotations

Entry Information
Gene NameC8orf44-SGK3 readthrough
Protein EntrySGK3_HUMAN
UniProt IDQ96BR1
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q96BR1-1; Sequence=Displayed; Name=2; IsoId=Q96BR1-2; Sequence=VSP_041903;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
Enzyme RegulationTwo 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.
FunctionSerine/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. {ECO:0000269|PubMed:12054501, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12632189, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16888620, ECO:0000269|PubMed:17167223, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:19293151, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:21865597}.
InductionInduced by estrogen/ER in breast cancer cells. {ECO:0000269|PubMed:21084382}.
InteractionQ96J02:ITCH; NbExp=5; IntAct=EBI-2801236, EBI-1564678;
PtmActivated 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. {ECO:0000269|PubMed:10548550, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16790420, ECO:0000269|PubMed:16888620}.
Sequence CautionSequence=AAF12758.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityBelongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. {ECO:0000305}.
SimilarityContains 1 AGC-kinase C-terminal domain. {ECO:0000305}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 1 PX (phox homology) domain. {ECO:0000255|PROSITE-ProRule:PRU00147}.
Subcellular LocationCytoplasmic vesicle {ECO:0000250}. 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.
SubunitInteracts with GSK3B and FLII. Interacts with PDPK1 in a phosphorylation-dependent manner. {ECO:0000269|PubMed:12054501, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16888620, ECO:0000269|PubMed:19293151}.
Tissue SpecificityExpressed 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. {ECO:0000269|PubMed:21084382}.
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