dbPTM

SGK1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	SGK1_HUMAN
UniProt AC	O00141
Protein Name	Serine/threonine-protein kinase Sgk1
Gene Name	SGK1
Organism	Homo sapiens (Human).
Sequence Length	431
Subcellular Localization	Cytoplasm. Nucleus. Endoplasmic reticulum membrane. Cell membrane. Mitochondrion. 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 s
Protein Description	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..
Protein Sequence	MTVKTEAAKGTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIANNSYACKHPEVQSILKISQPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAEEVFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYINGGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIEHNSTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQLKPNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHVFFSLINWDDLINKKITPPFNPNVSGPNDLRHFDPEFTEEPVPNSIGKSPDSVLVTASVKEAAEAFLGFSYAPPTDSFL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
41	Acetylation	GLNDFIQKIANNSYA CHHHHHHHHHCCCCC	38.68	30592363
50	Ubiquitination	ANNSYACKHPEVQSI HCCCCCCCCHHHHHH	54.76	-
56	Phosphorylation	CKHPEVQSILKISQP CCCHHHHHHHHCCCC	34.76	24719451
61	Phosphorylation	VQSILKISQPQEPEL HHHHHHCCCCCCHHH	33.93	23090842
74	Phosphorylation	ELMNANPSPPPSPSQ HHCCCCCCCCCCHHH	50.25	25159151
78	Phosphorylation	ANPSPPPSPSQQINL CCCCCCCCHHHCCCC	42.85	25159151
80	Phosphorylation	PSPPPSPSQQINLGP CCCCCCHHHCCCCCC	38.77	23090842
88	Phosphorylation	QQINLGPSSNPHAKP HCCCCCCCCCCCCCC	40.73	23090842
89	Phosphorylation	QINLGPSSNPHAKPS CCCCCCCCCCCCCCC	58.47	23090842
94	Ubiquitination	PSSNPHAKPSDFHFL CCCCCCCCCCCCEEE	41.86	-
102	Ubiquitination	PSDFHFLKVIGKGSF CCCCEEEEEECCCCH	30.75	-
111	Ubiquitination	IGKGSFGKVLLARHK ECCCCHHHHHHHHHC	27.91	-
118	Ubiquitination	KVLLARHKAEEVFYA HHHHHHHCHHHHHHH	52.52	-
124	Phosphorylation	HKAEEVFYAVKVLQK HCHHHHHHHHHHHHH	18.70	-
127	Ubiquitination	EEVFYAVKVLQKKAI HHHHHHHHHHHHHHH	29.11	-
145	Phosphorylation	KEEKHIMSERNVLLK HHHHHHHHHHHHHHH	32.57	29457462
152	Ubiquitination	SERNVLLKNVKHPFL HHHHHHHHHCCCCEE	56.38	-
252	Phosphorylation	KENIEHNSTTSTFCG HHHCCCCCCCCCCCC	34.66	29978859
253	Phosphorylation	ENIEHNSTTSTFCGT HHCCCCCCCCCCCCC	30.04	29978859
254	Phosphorylation	NIEHNSTTSTFCGTP HCCCCCCCCCCCCCH	26.12	29978859
255	Phosphorylation	IEHNSTTSTFCGTPE CCCCCCCCCCCCCHH	21.41	25627689
256	Phosphorylation	EHNSTTSTFCGTPEY CCCCCCCCCCCCHHH	22.35	25159151
260	Phosphorylation	TTSTFCGTPEYLAPE CCCCCCCCHHHHCHH	17.71	29978859
263	Phosphorylation	TFCGTPEYLAPEVLH CCCCCHHHHCHHHHH	14.90	22817900
271	Ubiquitination	LAPEVLHKQPYDRTV HCHHHHHCCCCCCCH	49.13	-
317	Ubiquitination	LNKPLQLKPNITNSA HCCCCCCCCCCHHHH	24.06	-
343	Ubiquitination	RTKRLGAKDDFMEIK HHHHCCCCCCHHHHH	56.91	-
367	Ubiquitination	WDDLINKKITPPFNP HHHHHCCCCCCCCCC	47.53	-
369	Phosphorylation	DLINKKITPPFNPNV HHHCCCCCCCCCCCC	33.51	11956329
377	Phosphorylation	PPFNPNVSGPNDLRH CCCCCCCCCCCCCCC	55.99	12023960
390	Phosphorylation	RHFDPEFTEEPVPNS CCCCCCCCCCCCCCC	37.46	22210691
397	Phosphorylation	TEEPVPNSIGKSPDS CCCCCCCCCCCCCCC	27.01	29255136
400	Ubiquitination	PVPNSIGKSPDSVLV CCCCCCCCCCCCEEE	58.08	-
401	Phosphorylation	VPNSIGKSPDSVLVT CCCCCCCCCCCEEEE	28.82	29255136
404	Phosphorylation	SIGKSPDSVLVTASV CCCCCCCCEEEEECH	22.27	22167270
408	Phosphorylation	SPDSVLVTASVKEAA CCCCEEEEECHHHHH	14.73	22167270
410	Phosphorylation	DSVLVTASVKEAAEA CCEEEEECHHHHHHH	25.10	22167270
422	Phosphorylation	AEAFLGFSYAPPTDS HHHHHCCCCCCCCCC	20.70	19232516

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
78	S	Phosphorylation	Kinase	MK07	Q13164	PhosphoELM
256	T	Phosphorylation	Kinase	PIK3C2A	O00443	PSP
256	T	Phosphorylation	Kinase	PDK1	Q15118	GPS
256	T	Phosphorylation	Kinase	PDK2	Q15119	PhosphoELM
256	T	Phosphorylation	Kinase	PDK1	O15530	PSP
369	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
369	T	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
369	T	Phosphorylation	Kinase	PKA	-	Uniprot
369	T	Phosphorylation	Kinase	PKA_GROUP	-	PhosphoELM
377	S	Phosphorylation	Kinase	NEK6	Q9HC98	PSP
422	S	Phosphorylation	Kinase	MTOR	P42345	PSP
422	S	Phosphorylation	Kinase	NEK6	Q9HC98	PSP
422	S	Phosphorylation	Kinase	PDK1	Q15118	GPS
422	S	Phosphorylation	Kinase	PDK2	Q15119	PhosphoELM
422	S	Phosphorylation	Kinase	PDPK1	O15530	PhosphoELM
422	S	Phosphorylation	Kinase	SGK1	O00141	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	RICTOR	Q6R327	PMID:20832730
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:16895519
-	K	Ubiquitination	E3 ubiquitin ligase	SYVN1	Q86TM6	PMID:16847254
-	K	Ubiquitination	E3 ubiquitin ligase	NEDD4L	Q96PU5	PMID:15576372

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
78	S	Phosphorylation	11254654
Phosphorylation on Ser-78 by MAPK7 is required for growth factor-induced cell cycle progression.
256	T	Phosphorylation	10191262
Activated by phosphorylation on Ser-422 by mTORC2, transforming it into a substrate for PDPK1 which phosphorylates it on Thr-256.
397	S	Phosphorylation	18691976
Phosphorylation on Ser-397 and Ser-401 are also essential for its activity.
401	S	Phosphorylation	18691976
Phosphorylation on Ser-397 and Ser-401 are also essential for its activity.
422	S	Phosphorylation	10191262
Activated by phosphorylation on Ser-422 by mTORC2, transforming it into a substrate for PDPK1 which phosphorylates it on Thr-256.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of SGK1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CDC37_HUMAN	CDC37	physical	17353931
TRFL_HUMAN	LTF	physical	17353931
EFTU_HUMAN	TUFM	physical	17353931
TERA_HUMAN	VCP	physical	17353931
SYIC_HUMAN	IARS	physical	17353931
PA2G4_HUMAN	PA2G4	physical	17353931
PIGR_HUMAN	PIGR	physical	17353931
IMA1_HUMAN	KPNA2	physical	12631736
KKCC2_HUMAN	CAMKK2	physical	12628440
MK07_HUMAN	MAPK7	physical	11254654
NHRF2_HUMAN	SLC9A3R2	physical	12387817
PDPK1_HUMAN	PDPK1	physical	12387817
NEDD4_HUMAN	NEDD4	physical	11696533
CHSP1_HUMAN	CARHSP1	physical	15910284
NHRF2_HUMAN	SLC9A3R2	physical	11751930
AF9_HUMAN	MLLT3	physical	17332896
RICTR_HUMAN	RICTOR	physical	20832730
SYVN1_HUMAN	SYVN1	physical	20947508
CHIP_HUMAN	STUB1	physical	20947508
T22D3_HUMAN	TSC22D3	physical	20947508
RAF1_HUMAN	RAF1	physical	20947508
CHIP_HUMAN	STUB1	physical	16895519
HSP74_HUMAN	HSPA4	physical	16895519
NED4L_HUMAN	NEDD4L	physical	16716084
RAF1_HUMAN	RAF1	physical	19380724
T22D3_HUMAN	TSC22D3	physical	19380724
WNK4_HUMAN	WNK4	physical	20525693
NED4L_HUMAN	NEDD4L	physical	20525693
NED4L_HUMAN	NEDD4L	physical	20730100
NEDD4_HUMAN	NEDD4	physical	20730100
NED4L_HUMAN	NEDD4L	physical	16006511
TAU_HUMAN	MAPT	physical	17512525
PRAF1_MOUSE	Rabac1	physical	20368287
TM109_MOUSE	Tmem109	physical	20368287
MAGA1_HUMAN	MAGEA1	physical	20368287
NED4L_HUMAN	NEDD4L	physical	23589291
T184C_HUMAN	TMEM184C	physical	21988832
TAU_HUMAN	MAPT	physical	15650334
1433Z_HUMAN	YWHAZ	physical	15650334
1433T_HUMAN	YWHAQ	physical	15650334
RPTOR_HUMAN	RPTOR	physical	18570873
MTOR_HUMAN	MTOR	physical	18570873
AKTS1_HUMAN	AKT1S1	physical	18570873
CDN1B_HUMAN	CDKN1B	physical	18570873
NDRG1_HUMAN	NDRG1	physical	19402821
SGK1_HUMAN	SGK1	physical	25384981
NED4L_HUMAN	NEDD4L	physical	19917253
ARL5B_HUMAN	ARL5B	physical	26186194
MYH14_HUMAN	MYH14	physical	26186194
FKBP5_HUMAN	FKBP5	physical	26186194
RAP2A_HUMAN	RAP2A	physical	26186194
PCCA_HUMAN	PCCA	physical	26186194
PIN1_HUMAN	PIN1	physical	25667458
LPP60_HUMAN	ASPG	physical	21063096
FKBP5_HUMAN	FKBP5	physical	28514442
RASH_HUMAN	HRAS	physical	28514442
ARL5B_HUMAN	ARL5B	physical	28514442

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of SGK1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"mTOR complex-2 activates ENaC by phosphorylating SGK1."; Lu M., Wang J., Jones K.T., Ives H.E., Feldman M.E., Yao L.J.,Shokat K.M., Ashrafi K., Pearce D.; J. Am. Soc. Nephrol. 21:811-818(2010). Cited for: PHOSPHORYLATION AT SER-422 BY MTORC2, AND INTERACTION WITH MTORC2.	20338997 [Abstract]
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74; SER-78; SER-397 ANDSER-401, AND MASS SPECTROMETRY.	19369195 [Abstract]
"Regulation of a third conserved phosphorylation site in SGK1."; Chen W., Chen Y., Xu B.E., Juang Y.C., Stippec S., Zhao Y., Cobb M.H.; J. Biol. Chem. 284:3453-3460(2009). Cited for: PHOSPHORYLATION AT SER-397 AND SER-401.	19068477 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74; SER-78; SER-397 ANDSER-401, AND MASS SPECTROMETRY.	18691976 [Abstract]
"mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylationand activation of serum- and glucocorticoid-induced protein kinase 1(SGK1)."; Garcia-Martinez J.M., Alessi D.R.; Biochem. J. 416:375-385(2008). Cited for: PHOSPHORYLATION AT SER-422 BY MTORC2.	18925875 [Abstract]
"BMK1 mediates growth factor-induced cell proliferation through directcellular activation of serum and glucocorticoid-inducible kinase."; Hayashi M., Tapping R.I., Chao T.H., Lo J.F., King C.C., Yang Y.,Lee J.D.; J. Biol. Chem. 276:8631-8634(2001). Cited for: PHOSPHORYLATION AT SER-78 BY MAPK7, AND INTERACTION WITH MAPK7.	11254654 [Abstract]
"Activation of serum- and glucocorticoid-regulated protein kinase byagonists that activate phosphatidylinositide 3-kinase is mediated by3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2."; Kobayashi T., Cohen P.; Biochem. J. 339:319-328(1999). Cited for: PHOSPHORYLATION AT THR-256 AND SER-422, AND MUTAGENESIS OF THR-256 ANDSER-422.	10191262 [Abstract]
"Activation of serum- and glucocorticoid-induced protein kinase (Sgk)by cyclic AMP and insulin."; Perrotti N., He R.A., Phillips S.A., Haft C.R., Taylor S.I.; J. Biol. Chem. 276:9406-9412(2001). Cited for: PHOSPHORYLATION AT THR-369 BY PKA.	11096081 [Abstract]

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