InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SGK1

Summary

InnateDB Protein

IDBP-96783.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SGK1

Protein Name

serum/glucocorticoid regulated kinase 1

Synonyms

SGK;

Species

Homo sapiens

Ensembl Protein

ENSP00000237305

InnateDB Gene

IDBG-96775 (SGK1)

Protein Structure

UniProt Annotation

Function

Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1. {ECO:0000269PubMed:11154281, ECO:0000269PubMed:11410590, ECO:0000269PubMed:11696533, ECO:0000269PubMed:12397388, ECO:0000269PubMed:12590200, ECO:0000269PubMed:12634932, ECO:0000269PubMed:12650886, ECO:0000269PubMed:12761204, ECO:0000269PubMed:12911626, ECO:0000269PubMed:14623317, ECO:0000269PubMed:14706641, ECO:0000269PubMed:15040001, ECO:0000269PubMed:15044175, ECO:0000269PubMed:15234985, ECO:0000269PubMed:15319523, ECO:0000269PubMed:15496163, ECO:0000269PubMed:15733869, ECO:0000269PubMed:15737648, ECO:0000269PubMed:15845389, ECO:0000269PubMed:15888551, ECO:0000269PubMed:16036218, ECO:0000269PubMed:16443776, ECO:0000269PubMed:16982696, ECO:0000269PubMed:17382906, ECO:0000269PubMed:18005662, ECO:0000269PubMed:18304449, ECO:0000269PubMed:18753299, ECO:0000269PubMed:19447520, ECO:0000269PubMed:19756449, ECO:0000269PubMed:20511718, ECO:0000269PubMed:20730100, ECO:0000269PubMed:21865597}.

Subcellular Localization

Cytoplasm. Nucleus. Endoplasmic reticulum membrane. Cell membrane. Mitochondrion. Note=The subcellular localization is controlled by the cell cycle, as well as by exposure to specific hormones and environmental stress stimuli. In proliferating cells, it shuttles between the nucleus and cytoplasm in synchrony with the cell cycle, and in serum/growth factor- stimulated cells it resides in the nucleus. In contrast, after exposure to environmental stress or treatment with glucocorticoids, it is detected in the cytoplasm and with certain stress conditions is associated with the mitochondria. In osmoregulation through the epithelial sodium channel, it can be localized to the cytoplasmic surface of the cell membrane. Nuclear, upon phosphorylation.Isoform 2: Cell membrane.

Disease Associations

Tissue Specificity

Expressed in most tissues with highest levels in the pancreas, followed by placenta, kidney and lung. Isoform 2 is strongly expressed in brain and pancreas, weaker in heart, placenta, lung, liver and skeletal muscle. {ECO:0000269PubMed:10548550, ECO:0000269PubMed:18753299}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 78 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	78 [view]
Protein-Protein	75 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005246	calcium channel regulator activity
GO:0005524	ATP binding
GO:0015459	potassium channel regulator activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017080	sodium channel regulator activity
GO:0017081	chloride channel regulator activity
GO:0035091	phosphatidylinositol binding

Biological Process

GO:0001558	regulation of cell growth
GO:0006468	protein phosphorylation
GO:0006814	sodium ion transport
GO:0006915	apoptotic process
GO:0006950	response to stress
GO:0007616	long-term memory
GO:0008217	regulation of blood pressure
GO:0030334	regulation of cell migration
GO:0032411	positive regulation of transporter activity
GO:0034220	ion transmembrane transport
GO:0042127	regulation of cell proliferation
GO:0042981	regulation of apoptotic process
GO:0050790	regulation of catalytic activity
GO:0051090	regulation of sequence-specific DNA binding transcription factor activity
GO:0055085	transmembrane transport
GO:0060453	regulation of gastric acid secretion
GO:0070294	renal sodium ion absorption

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005789	endoplasmic reticulum membrane
GO:0005829	cytosol
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001683 Phox homologous domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR017892 Protein kinase, C-terminal
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00787
PF00433

PRINTS

PR00109

PIRSF

SMART

SM00133
SM00312
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt