Q9ERE3 (SGK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	496 AA.
Sequence status	Complete.
Protein existence	Evidence 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.8 Ref.9 Ref.10
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 co-localization with the kinase responsible for phosphorylating Ser-486 thus allowing PDPK1 phosphorylation of Thr-320 resulting in complete activation of SGK3. Co-localizes with SLC9A3/NHE3 in the recycling endosomes By similarity. Localized in vesicle-like structures and in the early endosome. Ref.10
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.

Ontologies

Keywords
Cellular component	Cytoplasmic vesicle Endosome
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell communication Inferred from electronic annotation. Source: InterPro negative regulation of apoptotic process Inferred from direct assay Ref.1. Source: MGI
Cellular_component	cytoplasmic membrane-bounded vesicle Inferred from direct assay Ref.1. Source: MGI early endosome Inferred from electronic annotation. Source: UniProtKB-SubCell recycling endosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol binding Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 496

496

Serine/threonine-protein kinase Sgk3

PRO_0000086650

Regions

Domain

12 – 124

113

PX

Domain

162 – 419

258

Protein kinase

Domain

420 – 496

77

AGC-kinase C-terminal

Nucleotide binding

168 – 176

9

ATP By similarity

Motif

195 – 205

11

Nuclear localization signal By similarity

Sites

Active site

286

1

Proton acceptor By similarity

Binding site

191

1

ATP By similarity

Amino acid modifications

Modified residue

126

1

Phosphoserine Ref.6 Ref.7

Modified residue

129

1

Phosphoserine Ref.6 Ref.7

Modified residue

320

1

Phosphothreonine; by PDPK1 By similarity

Modified residue

486

1

Phosphoserine By similarity

Experimental info

Mutagenesis

90

1

R → A: Diminishes binding to phosphoinositides. Ref.3

Mutagenesis

191

1

K → A: No activity. Ref.1

Sequence conflict

114

1

R → G in BAC27349. Ref.2

Sequence conflict

204

1

Q → P in BAC27349. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

496

Helix Strand Turn

Details...

Beta strand

15 – 26

12

Beta strand

29 – 40

12

Beta strand

43 – 50

8

Helix

51 – 64

14

Helix

66 – 68

3

Helix

84 – 101

18

Helix

105 – 108

4

Helix

111 – 116

6

Turn

117 – 120

4

Helix

122 – 124

3

Sequences

	Sequence		Length	Mass (Da)
	Q9ERE3 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 4B7D2804A5948BAD	FASTA	496	57,145
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126 AND SER-129, MASS SPECTROMETRY. Tissue: Melanoma.
[7]	"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, MASS SPECTROMETRY. Tissue: Macrophage.
[8]	"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.
[9]	"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.
[10]	"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.

IPI

IPI00112303.

RefSeq

NP_001032848.1. NM_001037759.1.
NP_573483.1. NM_133220.2.
NP_808215.2. NM_177547.3.

UniGene

Mm.336410.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XTE	X-ray	1.60	A	7-160	[»]
1XTN	X-ray	2.20	A/B	7-126	[»]

ProteinModelPortal

Q9ERE3.

SMR

Q9ERE3. Positions 10-490.

ModBase

Search...

PTM databases

PhosphoSite

Q9ERE3.

Proteomic databases

PaxDb

Q9ERE3.

PRIDE

Q9ERE3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000097826; ENSMUSP00000095437; ENSMUSG00000025915.
ENSMUST00000166384; ENSMUSP00000130078; ENSMUSG00000025915.
ENSMUST00000168907; ENSMUSP00000126861; ENSMUSG00000025915.
ENSMUST00000171265; ENSMUSP00000127462; ENSMUSG00000025915.

GeneID

170755.

KEGG

mmu:170755.

UCSC

uc007agu.1. mouse.

Organism-specific databases

CTD

23678.

MGI

MGI:2182368. Sgk3.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00700000104132.

HOGENOM

HOG000233033.

HOVERGEN

HBG108317.

InParanoid

Q9ERE3.

KO

K13304.

OMA

HPELYNH.

Gene expression databases

ArrayExpress

Q9ERE3.

Bgee

Q9ERE3.

CleanEx

MM_SGK3.

Genevestigator

Q9ERE3.

GermOnline

ENSMUSG00000025915. Mus musculus.

Family and domain databases

Gene3D

3.30.1520.10. 1 hit.

InterPro

IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001683. Phox.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
PF00787. PX. 1 hit.
[Graphical view]

SMART

SM00312. PX. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.
SSF64268. PX. 1 hit.

PROSITE

PS51285. 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]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9ERE3.

NextBio

370338.

SOURCE

Search...

Entry information

Entry name

SGK3_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program