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Protein

Serine/threonine-protein kinase Sgk3

Gene

SGK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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: GO_Central
  • sodium channel regulator activity Source: UniProtKB

GO - Biological processi

  • intracellular signal transduction Source: GO_Central
  • ion transmembrane transport Source: Reactome
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  • peptidyl-serine phosphorylation 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 DNA binding transcription factor activity Source: UniProtKB

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000104205.12
HGNCiHGNC:10812 SGK3
MIMi607591 gene
neXtProtiNX_Q96BR1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
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 residuei320Phosphothreonine; by PDPK12 Publications1
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

EPDiQ96BR1
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, 9 interactors
ELMiQ96BR1
IntActiQ96BR1, 6 interactors
MINTiQ96BR1
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

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
KOG2101 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00890000139324
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ96BR1
KOiK13304
OMAiFTEEMVP
OrthoDBiEOG091G06FF
PhylomeDBiQ96BR1
TreeFamiTF320906

Family and domain databases

CDDicd06870 PX_CISK, 1 hit
cd05604 STKc_SGK3, 1 hit
Gene3Di3.30.1520.10, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR037900 CISK_PX
IPR011009 Kinase-like_dom_sf
IPR001683 Phox
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR036871 PX_dom_sf
IPR008271 Ser/Thr_kinase_AS
IPR037709 SGK3_dom
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PF00787 PX, 1 hit
SMARTiView protein in SMART
SM00312 PX, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
SSF64268 SSF64268, 1 hit
PROSITEiView protein in 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

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 → P1 PublicationCorresponds to variant dbSNP:rs750700898Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiSGK3_HUMAN
AccessioniPrimary (citable) accession number: Q96BR1
Secondary accession number(s): A8K5W3
, B3KQC2, Q9P1Q7, Q9UKG5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 22, 2003
Last sequence update: December 1, 2001
Last modified: April 25, 2018
This is version 166 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health