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Q9ERE3 (SGK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase Sgk3

EC=2.7.11.1
Alternative name(s):
Cytokine-independent survival kinase
Serum/glucocorticoid-regulated kinase 3
Serum/glucocorticoid-regulated kinase-like
Gene names
Name:Sgk3
Synonyms:Cisk, Sgkl
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length496 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/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 Ca2+ 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. Ref.4 Ref.5 Ref.7 Ref.8 Ref.9

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Two 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.

Subunit structure

Interacts with GSK3B and FLII By similarity. Interacts with PDPK1 in a phosphorylation-dependent manner By similarity.

Subcellular location

Cytoplasmic vesicle. Early endosome. Recycling endosome By similarity. 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. Colocalizes with SLC9A3/NHE3 in the recycling endosomes By similarity. Localized in vesicle-like structures and in the early endosome. Ref.9

Tissue specificity

Widely expressed, predominantly in the heart, spleen and 7-day embryo.

Post-translational modification

Activated 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 By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 protein kinase domain.

Contains 1 PX (phox homology) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 496496Serine/threonine-protein kinase Sgk3
PRO_0000086650

Regions

Domain12 – 124113PX
Domain162 – 419258Protein kinase
Domain420 – 49677AGC-kinase C-terminal
Nucleotide binding168 – 1769ATP By similarity
Motif195 – 20511Nuclear localization signal By similarity

Sites

Active site2861Proton acceptor By similarity
Binding site1911ATP By similarity

Amino acid modifications

Modified residue1261Phosphoserine Ref.6
Modified residue1291Phosphoserine Ref.6
Modified residue3201Phosphothreonine; by PDPK1 By similarity
Modified residue4861Phosphoserine By similarity

Experimental info

Mutagenesis901R → A: Diminishes binding to phosphoinositides. Ref.3
Mutagenesis1911K → A: No activity. Ref.1
Sequence conflict1141R → G in BAC27349. Ref.2
Sequence conflict2041Q → P in BAC27349. Ref.2

Secondary structure

................... 496
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9ERE3 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 4B7D2804A5948BAD

FASTA49657,145
        10         20         30         40         50         60 
MQRDCIMDYK ESCPSVSIPS SDEHREKKKR FTVYKVLVSV GRSEWFVFRR YAEFDKLYNS 

        70         80         90        100        110        120 
LKKQFPAMAL KIPAKRIFGD NFDPDFIKQR RAGLNEFIQN LVRYPELYNH PDVRAFLQMD 

       130        140        150        160        170        180 
SPRHQSDPSE DEDERSTSKP HSTSRNINLG PTGNPHAKPT DFDFLKVIGK GSFGKVLLAK 

       190        200        210        220        230        240 
RKLDGKFYAV KVLQKKIVLN RKEQKHIMAE RNVLLKNVKH PFLVGLHYSF QTTEKLYFVL 

       250        260        270        280        290        300 
DFVNGGELFF HLQRERSFPE PRARFYAAEI ASALGYLHSI KIVYRDLKPE NILLDSMGHV 

       310        320        330        340        350        360 
VLTDFGLCKE GIAISDTTTT FCGTPEYLAP EVIRKQPYDN TVDWWCLGAV LYEMLYGLPP 

       370        380        390        400        410        420 
FYCRDVAEMY DNILHKPLNL RPGVSLTAWS ILEELLEKNR QNRLGAKEDF LEIQNHPFFE 

       430        440        450        460        470        480 
SLSWTDLVQK KIPPPFNPNV AGPDDIRNFD AVFTEETVPY SVCVSSDYSI VNASVLEADD 

       490 
AFVGFSYAPP SEDLFL 

« Hide

References

« Hide 'large scale' references
[1]"Identification of CISK, a new member of the SGK kinase family that promotes IL-3-dependent survival."
Liu D., Yang X., Songyang Z.
Curr. Biol. 10:1233-1236(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-191.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Amnion, Bone marrow, Forelimb and Spleen.
[3]"Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides."
Xu J., Liu D., Gill G., Songyang Z.
J. Cell Biol. 154:699-705(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS OF ARG-90.
[4]"Regulation of GluR1 abundance in murine hippocampal neurones by serum- and glucocorticoid-inducible kinase 3."
Strutz-Seebohm N., Seebohm G., Mack A.F., Wagner H.J., Just L., Skutella T., Lang U.E., Henke G., Striegel M., Hollmann M., Rouach N., Nicoll R.A., McCormick J.A., Wang J., Pearce D., Lang F.
J. Physiol. (Lond.) 565:381-390(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF GRIA1/GLUR1.
[5]"Glucocorticoid adrenal steroids and glucocorticoid-inducible kinase isoforms in the regulation of GluR6 expression."
Strutz-Seebohm N., Seebohm G., Shumilina E., Mack A.F., Wagner H.J., Lampert A., Grahammer F., Henke G., Just L., Skutella T., Hollmann M., Lang F.
J. Physiol. (Lond.) 565:391-401(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF GRIK2/GLUR6.
[6]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126 AND SER-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Regulation of gastric acid secretion by the serum and glucocorticoid inducible kinase isoform SGK3."
Pasham V., Rotte A., Bhandaru M., Eichenmueller M., Froehlich H., Mack A.F., Bobbala D., Yang W., Pearce D., Lang F.
J. Gastroenterol. 46:305-317(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Decreased bone density and increased phosphaturia in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase 3."
Bhandaru M., Kempe D.S., Rotte A., Capuano P., Pathare G., Sopjani M., Alesutan I., Tyan L., Huang D.Y., Siraskar B., Judenhofer M.S., Stange G., Pichler B.J., Biber J., Quintanilla-Martinez L., Wagner C.A., Pearce D., Foeller M., Lang F.
Kidney Int. 80:61-67(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids."
He P., Lee S.J., Lin S., Seidler U., Lang F., Fejes-Toth G., Naray-Fejes-Toth A., Yun C.C.
Mol. Biol. Cell 22:3812-3825(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF SLC9A3/NHE3, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF312007 mRNA. Translation: AAG34115.1.
AK030314 mRNA. Translation: BAC26895.1.
AK031133 mRNA. Translation: BAC27269.1.
AK031328 mRNA. Translation: BAC27349.1.
AK146561 mRNA. Translation: BAE27261.1.
AK151181 mRNA. Translation: BAE30182.1.
AK171120 mRNA. Translation: BAE42262.1.
AK171186 mRNA. Translation: BAE42298.1.
AK171959 mRNA. Translation: BAE42748.1.
AK172323 mRNA. Translation: BAE42945.1.
CCDSCCDS14816.1.
RefSeqNP_001032848.1. NM_001037759.1.
NP_573483.1. NM_133220.2.
NP_808215.2. NM_177547.3.
UniGeneMm.336410.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XTEX-ray1.60A7-160[»]
1XTNX-ray2.20A/B7-126[»]
ProteinModelPortalQ9ERE3.
SMRQ9ERE3. Positions 10-490.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ9ERE3.

Proteomic databases

PaxDbQ9ERE3.
PRIDEQ9ERE3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000097826; ENSMUSP00000095437; ENSMUSG00000025915.
ENSMUST00000166384; ENSMUSP00000130078; ENSMUSG00000025915.
ENSMUST00000168907; ENSMUSP00000126861; ENSMUSG00000025915.
ENSMUST00000171265; ENSMUSP00000127462; ENSMUSG00000025915.
GeneID170755.
KEGGmmu:170755.
UCSCuc007agu.1. mouse.

Organism-specific databases

CTD23678.
MGIMGI:2182368. Sgk3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115309.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidQ9ERE3.
KOK13304.
OMAHPELYNH.
OrthoDBEOG7Q5HCW.
PhylomeDBQ9ERE3.
TreeFamTF320906.

Gene expression databases

ArrayExpressQ9ERE3.
BgeeQ9ERE3.
CleanExMM_SGK3.
GenevestigatorQ9ERE3.

Family and domain databases

Gene3D3.30.1520.10. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001683. Phox.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
PF00787. PX. 1 hit.
[Graphical view]
SMARTSM00312. PX. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50195. PX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9ERE3.
NextBio370338.
PROQ9ERE3.
SOURCESearch...

Entry information

Entry nameSGK3_MOUSE
AccessionPrimary (citable) accession number: Q9ERE3
Secondary accession number(s): Q3UAY2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 22, 2003
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot