dbPAF Protein Information


Tag Content
dbPAF ID dbPAF-0000006
Uniprot Accession O00141; SGK1_HUMAN; B7UUP7; B7UUP8; B7UUP9; B7Z5B2; E1P583; Q5TCN2; Q5TCN3; Q5TCN4; Q5VY65; Q9UN56;
Genbank Protein ID NP_001137148.1; NP_001137149.1; NP_001137150.1; NP_001278924.1; NP_005618.2; XP_011534373.1;
Genbank Nucleotide ID NM_001143676.1; NM_001143677.1; NM_001143678.1; NM_001291995.1; NM_005627.3; XM_011536071.1;
Protein Name Serine/threonine-protein kinase Sgk1
Protein Synonyms/Alias Serum/glucocorticoid-regulated kinase 1;
Gene Name SGK1
Gene Synonyms/Alias SGK;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)
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.
Phosphorylation Sites
dbPAF PTMs: 12
PositionPeptidesSourceReferences ( PMIDs )
74ELMNANPSPPPSPSQdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoSitePlus;SysPTM 2.0;UniProt;curated18691976; 19369195; 16381945; 23193290; 18988627; 21081558;
78ANPSPPPSPSQQINLdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PHOSIDA;PhosphoSitePlus;SysPTM 2.0;curated11254654; 18691976; 19369195; 16381945; 23193290; 15917303;
80PSPPPSPSQQINLGPcurated25850435
124HKAEEVFYAVKVLQKPhosphoSitePlus22135298
255IEHNSTTSTFCGTPEcurated25627689
256EHNSTTSTFCGTPEYdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;curated10191262; 16381945; 23193290; 11096081; 11956329; 15917303;
263TFCGTPEYLAPEVLHcurated22817900
369DLINKKITPPFNPNVdbPTM 3.0;Phospho.ELM 9.0;PhosphoSitePlus11096081; 16381945; 23193290; 11956329; 22135298
377PPFNPNVSGPNDLRHdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus12023960; 16381945; 23193290; 18988627; 22135298
397TEEPVPNSIGKSPDSdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoSitePlus;SysPTM 2.0;UniProt;curated18691976; 19068477; 19369195; 16381945; 23193290; 20068231;
401VPNSIGKSPDSVLVTdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoSitePlus;SysPTM 2.0;UniProt;curated18691976; 19068477; 19369195; 16381945; 23193290; 20068231;
422AEAFLGFSYAPPTDSdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;UniProt10191262; 18925875; 20338997; 16381945; 23193290; 12023960;
Sequence
(Fasta)
MTVKTEAAKG TLTYSRMRGM VAILIAFMKQ RRMGLNDFIQ KIANNSYACK HPEVQSILKI 60
SQPQEPELMN ANPSPPPSPS QQINLGPSSN PHAKPSDFHF LKVIGKGSFG KVLLARHKAE 120
EVFYAVKVLQ KKAILKKKEE KHIMSERNVL LKNVKHPFLV GLHFSFQTAD KLYFVLDYIN 180
GGELFYHLQR ERCFLEPRAR FYAAEIASAL GYLHSLNIVY RDLKPENILL DSQGHIVLTD 240
FGLCKENIEH NSTTSTFCGT PEYLAPEVLH KQPYDRTVDW WCLGAVLYEM LYGLPPFYSR 300
NTAEMYDNIL NKPLQLKPNI TNSARHLLEG LLQKDRTKRL GAKDDFMEIK SHVFFSLINW 360
DDLINKKITP PFNPNVSGPN DLRHFDPEFT EEPVPNSIGK SPDSVLVTAS VKEAAEAFLG 420
FSYAPPTDSF L 432
Keyword

KW-0002--3D-structure
KW-0877--Alternative promoter usage
KW-0025--Alternative splicing
KW-0053--Apoptosis
KW-0067--ATP-binding
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-1015--Disulfide bond
KW-0256--Endoplasmic reticulum
KW-0418--Kinase
KW-0472--Membrane
KW-0496--Mitochondrion
KW-0547--Nucleotide-binding
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0723--Serine/threonine-protein kinase
KW-0346--Stress response
KW-0808--Transferase
KW-0832--Ubl conjugation

Interpro

IPR000961--AGC-kinase_C
IPR011009--Kinase-like_dom
IPR017892--Pkinase_C
IPR000719--Prot_kinase_dom
IPR017441--Protein_kinase_ATP_BS
IPR002290--Ser/Thr_dual-sp_kinase
IPR008271--Ser/Thr_kinase_AS

PROSITE

PS51285--AGC_KINASE_CTER
PS00107--PROTEIN_KINASE_ATP
PS50011--PROTEIN_KINASE_DOM
PS00108--PROTEIN_KINASE_ST

Pfam

PF00069--Pkinase
PF00433--Pkinase_C

Gene Ontology

GO:0005737--C:cytoplasm
GO:0005829--C:cytosol
GO:0005789--C:endoplasmic reticulum membrane
GO:0005739--C:mitochondrion
GO:0005654--C:nucleoplasm
GO:0005886--C:plasma membrane
GO:0005524--F:ATP binding
GO:0005246--F:calcium channel regulator activity
GO:0017081--F:chloride channel regulator activity
GO:0015459--F:potassium channel regulator activity
GO:0004674--F:protein serine/threonine kinase activity
GO:0004712--F:protein serine/threonine/tyrosine kinase activity
GO:0017080--F:sodium channel regulator activity
GO:0006915--P:apoptotic process
GO:0006974--P:cellular response to DNA damage stimulus
GO:0006883--P:cellular sodium ion homeostasis
GO:0035556--P:intracellular signal transduction
GO:0034220--P:ion transmembrane transport
GO:0007616--P:long-term memory
GO:0048812--P:neuron projection morphogenesis
GO:0018105--P:peptidyl-serine phosphorylation
GO:0010765--P:positive regulation of sodium ion transport
GO:0032411--P:positive regulation of transporter activity
GO:0006468--P:protein phosphorylation
GO:0042981--P:regulation of apoptotic process
GO:0008217--P:regulation of blood pressure
GO:0050790--P:regulation of catalytic activity
GO:0001558--P:regulation of cell growth
GO:0030334--P:regulation of cell migration
GO:0042127--P:regulation of cell proliferation
GO:0060453--P:regulation of gastric acid secretion
GO:0051090--P:regulation of sequence-specific DNA binding transcription factor activity
GO:0070294--P:renal sodium ion absorption
GO:0006950--P:response to stress
GO:0006814--P:sodium ion transport
GO:0055085--P:transmembrane transport