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Protein

Serine/threonine-protein kinase Sgk3

Gene

Sgk3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei191 – 1911ATPPROSITE-ProRule annotation
Active sitei286 – 2861Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi168 – 1769ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
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 namesi
Name:Sgk3
Synonyms:Cisk, Sgkl
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620242. Sgk3.

Subcellular locationi

  • Cytoplasmic vesicle By similarity
  • Early endosome By similarity
  • 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. Localized in vesicle-like structures and in the early endosome. Colocalizes with SLC9A3/NHE3 in the recycling endosomes (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 496496Serine/threonine-protein kinase Sgk3PRO_0000263053Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei126 – 1261PhosphoserineBy similarity
Modified residuei129 – 1291PhosphoserineBy similarity
Modified residuei142 – 1421PhosphoserineBy similarity
Modified residuei320 – 3201Phosphothreonine; by PDPK1By similarity
Modified residuei461 – 4611PhosphoserineBy similarity
Modified residuei465 – 4651PhosphoserineBy similarity
Modified residuei486 – 4861PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8R4V0.
PRIDEiQ8R4V0.

PTM databases

iPTMnetiQ8R4V0.
PhosphoSiteiQ8R4V0.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000064540.

Structurei

3D structure databases

ProteinModelPortaliQ8R4V0.
SMRiQ8R4V0. Positions 10-125.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 124113PXPROSITE-ProRule annotationAdd
BLAST
Domaini162 – 464303Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini420 – 49677AGC-kinase C-terminalAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi195 – 20511Nuclear localization signalBy similarityAdd
BLAST

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
KOG2101. Eukaryota.
ENOG410XNPH. LUCA.
HOVERGENiHBG108317.
InParanoidiQ8R4V0.
PhylomeDBiQ8R4V0.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001683. Phox.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
PF00787. PX. 1 hit.
[Graphical view]
SMARTiSM00312. PX. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEiPS51285. 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]

Sequencei

Sequence statusi: Complete.

Q8R4V0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRDCTMDYK ESCPSVSIPS SDEHREKKKR FTVYKVLVSV GRSEWFVFRR
60 70 80 90 100
YAEFDKLYNS LKKQFPAMAL KIPAKRIFGD NFDPDFIKQR RAGLNEFIQN
110 120 130 140 150
LVRYPELYNH PDVRAFLQMD SPRHQSDPSE DEDERSTPKP HSTSRNINLG
160 170 180 190 200
PTGNPHAKPS DFDFLKVIGK GSFGKVLLAK RKLDGKFYAV KVLQKKIVLN
210 220 230 240 250
RKEQKHIMAE RNVLLKNVKH PFLVGLHYSF QTTEKLYFVL DFVNGGELFF
260 270 280 290 300
HLQRERSFPE PRARFYAAEI ASALGYLHSI KIVYRDLKPE NILLDSMGHV
310 320 330 340 350
VLTDFGLCKE GIAISDTTTT FCGTPEYLAP EVIRKQPYDR TVDWWCLGAV
360 370 380 390 400
LYEMLYGLPP FYCRDVAEMY DNILHKPLNL RPGVSLTAWS ILEELLEKNR
410 420 430 440 450
QNRLGAKEDF LEIQNHPFFE SLSWTDLVQK KIPPPFNPNV AGPDDIRNFD
460 470 480 490
AVFTEETVPY SVCVSSDYSI VNASVLEADD AFVGFSYAPP SEDLFL
Length:496
Mass (Da):57,171
Last modified:December 12, 2006 - v2
Checksum:i4D3B4F2E74078A47
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03002244 Genomic DNA. No translation available.
AF361755 mRNA. Translation: AAL91350.1.
UniGeneiRn.195351.
Rn.231796.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03002244 Genomic DNA. No translation available.
AF361755 mRNA. Translation: AAL91350.1.
UniGeneiRn.195351.
Rn.231796.

3D structure databases

ProteinModelPortaliQ8R4V0.
SMRiQ8R4V0. Positions 10-125.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000064540.

PTM databases

iPTMnetiQ8R4V0.
PhosphoSiteiQ8R4V0.

Proteomic databases

PaxDbiQ8R4V0.
PRIDEiQ8R4V0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

RGDi620242. Sgk3.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
KOG2101. Eukaryota.
ENOG410XNPH. LUCA.
HOVERGENiHBG108317.
InParanoidiQ8R4V0.
PhylomeDBiQ8R4V0.

Miscellaneous databases

PROiQ8R4V0.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001683. Phox.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
PF00787. PX. 1 hit.
[Graphical view]
SMARTiSM00312. PX. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEiPS51285. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiSGK3_RAT
AccessioniPrimary (citable) accession number: Q8R4V0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: December 12, 2006
Last modified: July 6, 2016
This is version 85 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.