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Q9HBY8 (SGK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase Sgk2

EC=2.7.11.1
Alternative name(s):
Serum/glucocorticoid-regulated kinase 2
Gene names
Name:SGK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 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, survival and proliferation. Up-regulates Na+ channels: SCNN1A/ENAC, K+ channels: KCNA3/Kv1.3, KCNE1 and KCNQ1, amino acid transporter: SLC6A19, glutamate transporter: SLC1A6/EAAT4, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na+/H+ exchanger: SLC9A3/NHE3, and the Na+/K+ ATPase. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Two specific sites, one in the kinase domain (Thr-253) and the other in the C-terminal regulatory region (Ser-416), need to be phosphorylated for its full activation.

Subcellular location

Cytoplasm. Nucleus Ref.12.

Tissue specificity

Highly expressed in liver, kidney and pancreas, and at lower levels in brain. Ref.1

Post-translational modification

Activated by phosphorylation on Ser-416 by an unknown kinase (may be mTORC2 but not confirmed), transforming it into a substrate for PDPK1 which then phosphorylates it on Thr-253.

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.

Caution

Not regulated by serum or glucocorticoids.

Ontologies

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: Q9HBY8-1)

Also known as: beta;

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.
Isoform 1 (identifier: Q9HBY8-2)

Also known as: alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: Missing.
Isoform 3 (identifier: Q9HBY8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     19-52: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 427427Serine/threonine-protein kinase Sgk2
PRO_0000086646

Regions

Domain95 – 352258Protein kinase
Domain353 – 42775AGC-kinase C-terminal
Nucleotide binding101 – 1099ATP By similarity
Motif128 – 13811Nuclear localization signal By similarity

Sites

Active site2191Proton acceptor By similarity
Binding site1241ATP By similarity

Amino acid modifications

Modified residue2531Phosphothreonine; by PDPK1 Ref.1
Modified residue4161Phosphoserine Potential

Natural variations

Alternative sequence1 – 6060Missing in isoform 1.
VSP_004932
Alternative sequence19 – 5234Missing in isoform 3.
VSP_026682
Natural variant121S → T. Ref.15
Corresponds to variant rs33969356 [ dbSNP | Ensembl ].
VAR_041073
Natural variant2591E → K in a lung adenocarcinoma sample; somatic mutation. Ref.15
VAR_041074
Natural variant3491H → Y. Ref.15
Corresponds to variant rs35793869 [ dbSNP | Ensembl ].
VAR_041075

Experimental info

Mutagenesis4161S → D: Increased activation. Ref.1
Sequence conflict1371Missing in CAI42315. Ref.4
Sequence conflict1681K → E in AAX88805. Ref.2
Sequence conflict2081G → D in AAV38901. Ref.3
Sequence conflict3371L → P in AAX88805. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (beta) [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: D8F0FA6DF54B1370

FASTA42747,604
        10         20         30         40         50         60 
MQGLLTSGRK PSGGGRCTGR GGWRGQWCLK PWMGGADPPT PTLSCLLLPV PPELPDHCYR 

        70         80         90        100        110        120 
MNSSPAGTPS PQPSRANGNI NLGPSANPNA QPTDFDFLKV IGKGNYGKVL LAKRKSDGAF 

       130        140        150        160        170        180 
YAVKVLQKKS ILKKKEQSHI MAERSVLLKN VRHPFLVGLR YSFQTPEKLY FVLDYVNGGE 

       190        200        210        220        230        240 
LFFHLQRERR FLEPRARFYA AEVASAIGYL HSLNIIYRDL KPENILLDCQ GHVVLTDFGL 

       250        260        270        280        290        300 
CKEGVEPEDT TSTFCGTPEY LAPEVLRKEP YDRAVDWWCL GAVLYEMLHG LPPFYSQDVS 

       310        320        330        340        350        360 
QMYENILHQP LQIPGGRTVA ACDLLQSLLH KDQRQRLGSK ADFLEIKNHV FFSPINWDDL 

       370        380        390        400        410        420 
YHKRLTPPFN PNVTGPADLK HFDPEFTQEA VSKSIGCTPD TVASSSGASS AFLGFSYAPE 


DDDILDC 

« Hide

Isoform 1 (alpha) [UniParc].

Checksum: E53F1ABE253F648B
Show »

FASTA36741,175
Isoform 3 [UniParc].

Checksum: DB7303AF95D844CE
Show »

FASTA39343,977

References

« Hide 'large scale' references
[1]"Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase."
Kobayashi T., Deak M., Morrice N., Cohen P.
Biochem. J. 344:189-197(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, PHOSPHORYLATION AT THR-253, MUTAGENESIS OF SER-416.
[2]Li H., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M., Xiao W., Lin L., Yang S.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain and Colon.
[6]"Activation of Na+/K+-ATPase by the serum and glucocorticoid-dependent kinase isoforms."
Henke G., Setiawan I., Boehmer C., Lang F.
Kidney Blood Press. Res. 25:370-374(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF NA(+)/K(+) ATPASE.
[7]"K(+) channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK."
Gamper N., Fillon S., Feng Y., Friedrich B., Lang P.A., Henke G., Huber S.M., Kobayashi T., Cohen P., Lang F.
Pflugers Arch. 445:60-66(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Regulation of KCNE1-dependent K(+) current by the serum and glucocorticoid-inducible kinase (SGK) isoforms."
Embark H.M., Boehmer C., Vallon V., Luft F., Lang F.
Pflugers Arch. 445:601-606(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF KCNE1 AND KCNQ1.
[9]"The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel alpha,beta,gamma-ENaC."
Friedrich B., Feng Y., Cohen P., Risler T., Vandewalle A., Broeer S., Wang J., Pearce D., Lang F.
Pflugers Arch. 445:693-696(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF SCNN1A/ENAC.
[10]"Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1."
Henke G., Maier G., Wallisch S., Boehmer C., Lang F.
J. Cell. Physiol. 199:194-199(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF KCNA3/KV1.3.
[11]"The serum and glucocorticoid inducible kinases SGK1-3 stimulate the neutral amino acid transporter SLC6A19."
Boehmer C., Sopjani M., Klaus F., Lindner R., Laufer J., Jeyaraj S., Lang F., Palmada M.
Cell. Physiol. Biochem. 25:723-732(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF SLC6A19.
[12]"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.
[13]"Sgk kinases and their role in epithelial transport."
Loffing J., Flores S.Y., Staub O.
Annu. Rev. Physiol. 68:461-490(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"Second AKT: the rise of SGK in cancer signalling."
Bruhn M.A., Pearson R.B., Hannan R.D., Sheppard K.E.
Growth Factors 28:394-408(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[15]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-12; LYS-259 AND TYR-349.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF169034 mRNA. Translation: AAF12757.2.
AF186470 mRNA. Translation: AAG17012.1.
AY987010 mRNA. Translation: AAX88805.1.
BT020098 mRNA. Translation: AAV38901.1.
Z98752 Genomic DNA. Translation: CAC18509.1.
Z98752 Genomic DNA. Translation: CAI42312.1.
Z98752 Genomic DNA. Translation: CAI42315.1.
BC014037 mRNA. Translation: AAH14037.3.
BC065511 mRNA. Translation: AAH65511.1.
CCDSCCDS13320.1. [Q9HBY8-1]
CCDS13321.1. [Q9HBY8-2]
RefSeqNP_001186193.1. NM_001199264.1. [Q9HBY8-2]
NP_057360.2. NM_016276.3. [Q9HBY8-1]
NP_733794.1. NM_170693.2. [Q9HBY8-2]
UniGeneHs.300863.
Hs.740147.

3D structure databases

ProteinModelPortalQ9HBY8.
SMRQ9HBY8. Positions 80-418.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115416. 7 interactions.
IntActQ9HBY8. 2 interactions.
STRING9606.ENSP00000340608.

Chemistry

ChEMBLCHEMBL5794.
GuidetoPHARMACOLOGY1535.

PTM databases

PhosphoSiteQ9HBY8.

Polymorphism databases

DMDM28558166.

Proteomic databases

MaxQBQ9HBY8.
PaxDbQ9HBY8.
PRIDEQ9HBY8.

Protocols and materials databases

DNASU10110.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000341458; ENSP00000340608; ENSG00000101049. [Q9HBY8-1]
ENST00000373092; ENSP00000362184; ENSG00000101049. [Q9HBY8-2]
ENST00000373100; ENSP00000362192; ENSG00000101049. [Q9HBY8-2]
ENST00000423407; ENSP00000392795; ENSG00000101049. [Q9HBY8-2]
ENST00000426287; ENSP00000412214; ENSG00000101049. [Q9HBY8-3]
GeneID10110.
KEGGhsa:10110.
UCSCuc002xkr.3. human. [Q9HBY8-1]

Organism-specific databases

CTD10110.
GeneCardsGC20P042187.
H-InvDBHIX0080189.
HGNCHGNC:13900. SGK2.
HPAHPA011387.
MIM607589. gene.
neXtProtNX_Q9HBY8.
PharmGKBPA37824.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidQ9HBY8.
KOK13303.
OMACQGHVVL.
OrthoDBEOG7Q5HCW.
PhylomeDBQ9HBY8.
TreeFamTF320906.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
SignaLinkQ9HBY8.

Gene expression databases

ArrayExpressQ9HBY8.
BgeeQ9HBY8.
CleanExHS_SGK2.
GenevestigatorQ9HBY8.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 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.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSGK2.
GenomeRNAi10110.
NextBio38243.
PROQ9HBY8.
SOURCESearch...

Entry information

Entry nameSGK2_HUMAN
AccessionPrimary (citable) accession number: Q9HBY8
Secondary accession number(s): Q52PK5 expand/collapse secondary AC list , Q5H8Y6, Q5H8Z1, Q5TZR3, Q9UKG6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 22, 2003
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM