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Protein

Serine/threonine-protein kinase Sgk3

Gene

SGK3

Organism
Homo sapiens (Human)
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.21 Publications

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)DescriptionActionsGraphical viewLength
Binding sitei191ATPPROSITE-ProRule annotation1
Active sitei286Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi168 – 176ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calcium channel regulator activity Source: UniProtKB
  • chloride channel regulator activity Source: UniProtKB
  • phosphatidylinositol binding Source: InterPro
  • potassium channel regulator activity Source: UniProtKB
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: ProtInc
  • sodium channel regulator activity Source: UniProtKB

GO - Biological processi

  • cellular sodium ion homeostasis Source: GO_Central
  • intracellular signal transduction Source: GO_Central
  • ion transmembrane transport Source: Reactome
  • peptidyl-serine phosphorylation Source: GO_Central
  • positive regulation of sodium ion transport Source: GO_Central
  • positive regulation of transporter activity Source: GO_Central
  • protein phosphorylation Source: ProtInc
  • regulation of apoptotic process Source: GO_Central
  • regulation of cell growth Source: UniProtKB
  • regulation of cell migration Source: UniProtKB
  • regulation of cell proliferation Source: UniProtKB
  • regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • response to stress Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS02552-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.
SignaLinkiQ96BR1.
SIGNORiQ96BR1.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:10812. SGK3.

Subcellular locationi

  • Cytoplasmic vesicle By similarity
  • Early endosome
  • Recycling endosome

  • 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.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi90R → A: Partially localized to the membrane. 1 Publication1
Mutagenesisi191K → M: Abolishes activity. 1 Publication1
Mutagenesisi486S → D: Increased activation. 1 Publication1

Organism-specific databases

DisGeNETi23678.
OpenTargetsiENSG00000104205.
ENSG00000270024.
PharmGKBiPA35722.

Chemistry databases

ChEMBLiCHEMBL6186.
GuidetoPHARMACOLOGYi1536.

Polymorphism and mutation databases

BioMutaiSGK3.
DMDMi28558163.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866491 – 496Serine/threonine-protein kinase Sgk3Add BLAST496

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei126PhosphoserineBy similarity1
Modified residuei129PhosphoserineBy similarity1
Modified residuei142PhosphoserineBy similarity1
Modified residuei320Phosphothreonine; by PDPK12 Publications1
Modified residuei461PhosphoserineBy similarity1
Modified residuei465PhosphoserineBy similarity1
Modified residuei486Phosphoserine2 Publications1

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-320.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ96BR1.
PaxDbiQ96BR1.
PeptideAtlasiQ96BR1.
PRIDEiQ96BR1.

PTM databases

iPTMnetiQ96BR1.
PhosphoSitePlusiQ96BR1.

Expressioni

Tissue specificityi

Expressed in most tissues with highest levels in pancreas, kidney liver, heart and brain and lower levels in lung, placenta and skeletal muscle. Expression is higher in ER-positive breast tumors than ER-negative breast tumors.1 Publication

Inductioni

Induced by estrogen/ER in breast cancer cells.1 Publication

Gene expression databases

BgeeiENSG00000104205.
CleanExiHS_SGK2.
HS_SGK3.
ExpressionAtlasiQ96BR1. baseline and differential.
GenevisibleiQ96BR1. HS.

Organism-specific databases

HPAiHPA027146.

Interactioni

Subunit structurei

Interacts with GSK3B and FLII. Interacts with PDPK1 in a phosphorylation-dependent manner.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ITCHQ96J025EBI-2801236,EBI-1564678

Protein-protein interaction databases

BioGridi117195. 8 interactors.
IntActiQ96BR1. 6 interactors.
MINTiMINT-2813751.
STRINGi9606.ENSP00000262211.

Chemistry databases

BindingDBiQ96BR1.

Structurei

3D structure databases

ProteinModelPortaliQ96BR1.
SMRiQ96BR1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 124PXPROSITE-ProRule annotationAdd BLAST113
Domaini162 – 419Protein kinasePROSITE-ProRule annotationAdd BLAST258
Domaini420 – 496AGC-kinase C-terminalAdd BLAST77

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi195 – 205Nuclear localization signalBy similarityAdd BLAST11

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.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ96BR1.
KOiK13304.
OMAiFTEEMVP.
OrthoDBiEOG091G06FF.
PhylomeDBiQ96BR1.
TreeFamiTF320906.

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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96BR1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQRDHTMDYK ESCPSVSIPS SDEHREKKKR FTVYKVLVSV GRSEWFVFRR
60 70 80 90 100
YAEFDKLYNT LKKQFPAMAL KIPAKRIFGD NFDPDFIKQR RAGLNEFIQN
110 120 130 140 150
LVRYPELYNH PDVRAFLQMD SPKHQSDPSE DEDERSSQKL HSTSQNINLG
160 170 180 190 200
PSGNPHAKPT DFDFLKVIGK GSFGKVLLAK RKLDGKFYAV KVLQKKIVLN
210 220 230 240 250
RKEQKHIMAE RNVLLKNVKH PFLVGLHYSF QTTEKLYFVL DFVNGGELFF
260 270 280 290 300
HLQRERSFPE HRARFYAAEI ASALGYLHSI KIVYRDLKPE NILLDSVGHV
310 320 330 340 350
VLTDFGLCKE GIAISDTTTT FCGTPEYLAP EVIRKQPYDN TVDWWCLGAV
360 370 380 390 400
LYEMLYGLPP FYCRDVAEMY DNILHKPLSL RPGVSLTAWS ILEELLEKDR
410 420 430 440 450
QNRLGAKEDF LEIQNHPFFE SLSWADLVQK KIPPPFNPNV AGPDDIRNFD
460 470 480 490
TAFTEETVPY SVCVSSDYSI VNASVLEADD AFVGFSYAPP SEDLFL
Length:496
Mass (Da):57,108
Last modified:December 1, 2001 - v1
Checksum:i76A6CCEB69006CF1
GO
Isoform 2 (identifier: Q96BR1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     327-358: Missing.

Show »
Length:464
Mass (Da):53,306
Checksum:iD5028F96C651C465
GO

Sequence cautioni

The sequence AAF12758 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti54F → V in AAF27051 (PubMed:10585774).Curated1
Sequence conflicti127D → G in AAF27051 (PubMed:10585774).Curated1
Sequence conflicti187F → V in AAF27051 (PubMed:10585774).Curated1
Sequence conflicti294L → V in AAF27051 (PubMed:10585774).Curated1
Sequence conflicti387T → R in AAF27051 (PubMed:10585774).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03563692A → V in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_041076355L → P.1 PublicationCorresponds to variant rs750700898dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041903327 – 358Missing in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169035 mRNA. Translation: AAF12758.1. Different initiation.
AF085233 mRNA. Translation: AAF27051.2.
AK074666 mRNA. Translation: BAG51984.1.
AK291428 mRNA. Translation: BAF84117.1.
AC011031 Genomic DNA. No translation available.
AC090154 Genomic DNA. No translation available.
CH471068 Genomic DNA. Translation: EAW86919.1.
BC015326 mRNA. Translation: AAH15326.1.
CCDSiCCDS6195.1. [Q96BR1-1]
CCDS6196.1. [Q96BR1-2]
RefSeqiNP_001028750.1. NM_001033578.2. [Q96BR1-1]
NP_001191102.1. NM_001204173.1. [Q96BR1-1]
NP_037389.4. NM_013257.4. [Q96BR1-1]
NP_733827.2. NM_170709.2. [Q96BR1-2]
UniGeneiHs.613417.
Hs.733251.

Genome annotation databases

EnsembliENST00000345714; ENSP00000331816; ENSG00000104205. [Q96BR1-1]
ENST00000396596; ENSP00000379842; ENSG00000104205. [Q96BR1-1]
ENST00000520976; ENSP00000430691; ENSG00000104205. [Q96BR1-2]
ENST00000521198; ENSP00000430463; ENSG00000104205. [Q96BR1-1]
ENST00000522398; ENSP00000430256; ENSG00000104205. [Q96BR1-1]
GeneIDi100533105.
23678.
KEGGihsa:100533105.
hsa:23678.
UCSCiuc003xwp.4. human. [Q96BR1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169035 mRNA. Translation: AAF12758.1. Different initiation.
AF085233 mRNA. Translation: AAF27051.2.
AK074666 mRNA. Translation: BAG51984.1.
AK291428 mRNA. Translation: BAF84117.1.
AC011031 Genomic DNA. No translation available.
AC090154 Genomic DNA. No translation available.
CH471068 Genomic DNA. Translation: EAW86919.1.
BC015326 mRNA. Translation: AAH15326.1.
CCDSiCCDS6195.1. [Q96BR1-1]
CCDS6196.1. [Q96BR1-2]
RefSeqiNP_001028750.1. NM_001033578.2. [Q96BR1-1]
NP_001191102.1. NM_001204173.1. [Q96BR1-1]
NP_037389.4. NM_013257.4. [Q96BR1-1]
NP_733827.2. NM_170709.2. [Q96BR1-2]
UniGeneiHs.613417.
Hs.733251.

3D structure databases

ProteinModelPortaliQ96BR1.
SMRiQ96BR1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117195. 8 interactors.
IntActiQ96BR1. 6 interactors.
MINTiMINT-2813751.
STRINGi9606.ENSP00000262211.

Chemistry databases

BindingDBiQ96BR1.
ChEMBLiCHEMBL6186.
GuidetoPHARMACOLOGYi1536.

PTM databases

iPTMnetiQ96BR1.
PhosphoSitePlusiQ96BR1.

Polymorphism and mutation databases

BioMutaiSGK3.
DMDMi28558163.

Proteomic databases

MaxQBiQ96BR1.
PaxDbiQ96BR1.
PeptideAtlasiQ96BR1.
PRIDEiQ96BR1.

Protocols and materials databases

DNASUi23678.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345714; ENSP00000331816; ENSG00000104205. [Q96BR1-1]
ENST00000396596; ENSP00000379842; ENSG00000104205. [Q96BR1-1]
ENST00000520976; ENSP00000430691; ENSG00000104205. [Q96BR1-2]
ENST00000521198; ENSP00000430463; ENSG00000104205. [Q96BR1-1]
ENST00000522398; ENSP00000430256; ENSG00000104205. [Q96BR1-1]
GeneIDi100533105.
23678.
KEGGihsa:100533105.
hsa:23678.
UCSCiuc003xwp.4. human. [Q96BR1-1]

Organism-specific databases

CTDi100533105.
23678.
DisGeNETi23678.
GeneCardsiSGK3.
HGNCiHGNC:10812. SGK3.
HPAiHPA027146.
MIMi607591. gene.
neXtProtiNX_Q96BR1.
OpenTargetsiENSG00000104205.
ENSG00000270024.
PharmGKBiPA35722.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
KOG2101. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ96BR1.
KOiK13304.
OMAiFTEEMVP.
OrthoDBiEOG091G06FF.
PhylomeDBiQ96BR1.
TreeFamiTF320906.

Enzyme and pathway databases

BioCyciZFISH:HS02552-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.
SignaLinkiQ96BR1.
SIGNORiQ96BR1.

Miscellaneous databases

GeneWikiiSGK3.
PROiQ96BR1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104205.
CleanExiHS_SGK2.
HS_SGK3.
ExpressionAtlasiQ96BR1. baseline and differential.
GenevisibleiQ96BR1. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q96BR1
Secondary accession number(s): A8K5W3
, B3KQC2, Q9P1Q7, Q9UKG5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 22, 2003
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.