Serine/threonine-protein kinase Sgk1 (EC 2.7.11.1) (Serum/glucocorticoid-regulated kinase 1)
1_MTVKT 6_ EAAKG 11_ TLTYS 16_ RMRGM 21_ VAILI 26_ AFMKQ 31_ RRMGL 36_ NDFIQ 41_ KIANN 46_ SYACK 51_ HPEVQ 56_ SILKI 61_ SQPQE 66_ PELMN 71_ ANPSP 76_ PPSPS 81_ QQINL 86_ GPSSN 91_ PHAKP 96_ SDFHF 101_ LKVIG 106_ KGSFG 111_ KVLLA 116_ RHKAE 121_ EVFYA 126_ VKVLQ 131_ KKAIL 136_ KKKEE 141_ KHIMS 146_ ERNVL 151_ LKNVK 156_ HPFLV 161_ GLHFS 166_ FQTAD 171_ KLYFV 176_ LDYIN 181_ GGELF 186_ YHLQR 191_ ERCFL 196_ EPRAR 201_ FYAAE 206_ IASAL 211_ GYLHS 216_ LNIVY 221_ RDLKP 226_ ENILL 231_ DSQGH 236_ IVLTD 241_ FGLCK 246_ ENIEH 251_ NSTTS 256_ TFCGT 261_ PEYLA 266_ PEVLH 271_ KQPYD 276_ RTVDW 281_ WCLGA 286_ VLYEM 291_ LYGLP 296_ PFYSR 301_ NTAEM 306_ YDNIL 311_ NKPLQ 316_ LKPNI 321_ TNSAR 326_ HLLEG 331_ LLQKD 336_ RTKRL 341_ GAKDD 346_ FMEIK 351_ SHVFF 356_ SLINW 361_ DDLIN 366_ KKITP 371_ PFNPN 376_ VSGPN 381_ DLRHF 386_ DPEFT 391_ EEPVP 396_ NSIGK 401_ SPDSV 406_ LVTAS 411_ VKEAA 416_ EAFLG 421_ FSYAP 426_PTDSF
1: 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