Q9HBY8 (SGK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase Sgk2
EC=2.7.11.1

Alternative name(s):
Serum/glucocorticoid-regulated kinase 2

Gene names

Name:

SGK2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	427 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, 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

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Traceable author statement Ref.1. Source: ProtInc positive regulation of transporter activity Traceable author statement Ref.13. Source: UniProtKB regulation of cell growth Traceable author statement Ref.14. Source: UniProtKB regulation of cell proliferation Traceable author statement Ref.14. Source: UniProtKB response to oxidative stress Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW potassium channel regulator activity Inferred from direct assay Ref.7. Source: UniProtKB protein serine/threonine kinase activity Traceable author statement Ref.1. Source: ProtInc sodium channel regulator activity Non-traceable author statement Ref.9. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 427	427	Serine/threonine-protein kinase Sgk2		PRO_0000086646
Regions
	Domain	95 – 352	258	Protein kinase
	Domain	353 – 427	75	AGC-kinase C-terminal
	Nucleotide binding	101 – 109	9	ATP By similarity
	Motif	128 – 138	11	Nuclear localization signal By similarity
Sites
	Active site	219	1	Proton acceptor By similarity
	Binding site	124	1	ATP By similarity
Amino acid modifications
	Modified residue	253	1	Phosphothreonine; by PDPK1 Ref.1
	Modified residue	416	1	Phosphoserine Potential
Natural variations
	Alternative sequence	1 – 60	60	Missing in isoform 1.		VSP_004932
	Alternative sequence	19 – 52	34	Missing in isoform 3.		VSP_026682
	Natural variant	12	1	S → T. Ref.15 Corresponds to variant rs33969356 [ dbSNP | Ensembl ].		VAR_041073
	Natural variant	259	1	E → K in a lung adenocarcinoma sample; somatic mutation. Ref.15		VAR_041074
	Natural variant	349	1	H → Y. Ref.15 Corresponds to variant rs35793869 [ dbSNP | Ensembl ].		VAR_041075
Experimental info
	Mutagenesis	416	1	S → D: Increased activation. Ref.1
	Sequence conflict	137	1	Missing in CAI42315. Ref.4
	Sequence conflict	168	1	K → E in AAX88805. Ref.2
	Sequence conflict	208	1	G → D in AAV38901. Ref.3
	Sequence conflict	337	1	L → P in AAX88805. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (beta) [UniParc]. Last modified March 1, 2001. Version 1. Checksum: D8F0FA6DF54B1370	FASTA	427	47,604
	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
	Isoform 1 (alpha) [UniParc]. Checksum: E53F1ABE253F648B	FASTA	367	41,175
	10 20 30 40 50 60 MNSSPAGTPS PQPSRANGNI NLGPSANPNA QPTDFDFLKV IGKGNYGKVL LAKRKSDGAF 70 80 90 100 110 120 YAVKVLQKKS ILKKKEQSHI MAERSVLLKN VRHPFLVGLR YSFQTPEKLY FVLDYVNGGE 130 140 150 160 170 180 LFFHLQRERR FLEPRARFYA AEVASAIGYL HSLNIIYRDL KPENILLDCQ GHVVLTDFGL 190 200 210 220 230 240 CKEGVEPEDT TSTFCGTPEY LAPEVLRKEP YDRAVDWWCL GAVLYEMLHG LPPFYSQDVS 250 260 270 280 290 300 QMYENILHQP LQIPGGRTVA ACDLLQSLLH KDQRQRLGSK ADFLEIKNHV FFSPINWDDL 310 320 330 340 350 360 YHKRLTPPFN PNVTGPADLK HFDPEFTQEA VSKSIGCTPD TVASSSGASS AFLGFSYAPE DDDILDC
	Isoform 3 [UniParc]. Checksum: DB7303AF95D844CE	FASTA	393	43,977
	10 20 30 40 50 60 MQGLLTSGRK PSGGGRCTEL PDHCYRMNSS PAGTPSPQPS RANGNINLGP SANPNAQPTD 70 80 90 100 110 120 FDFLKVIGKG NYGKVLLAKR KSDGAFYAVK VLQKKSILKK KEQSHIMAER SVLLKNVRHP 130 140 150 160 170 180 FLVGLRYSFQ TPEKLYFVLD YVNGGELFFH LQRERRFLEP RARFYAAEVA SAIGYLHSLN 190 200 210 220 230 240 IIYRDLKPEN ILLDCQGHVV LTDFGLCKEG VEPEDTTSTF CGTPEYLAPE VLRKEPYDRA 250 260 270 280 290 300 VDWWCLGAVL YEMLHGLPPF YSQDVSQMYE NILHQPLQIP GGRTVAACDL LQSLLHKDQR 310 320 330 340 350 360 QRLGSKADFL EIKNHVFFSP INWDDLYHKR LTPPFNPNVT GPADLKHFDP EFTQEAVSKS 370 380 390 IGCTPDTVAS SSGASSAFLG FSYAPEDDDI LDC

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00009887. IPI00217154. IPI00853438.
RefSeq	NP_001186193.1. NM_001199264.1. NP_057360.2. NM_016276.3. NP_733794.1. NM_170693.2.
UniGene	Hs.300863. Hs.740147.
3D structure databases
ProteinModelPortal	Q9HBY8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HBY8. 2 interactions.
STRING	9606.ENSP00000340608.
PTM databases
PhosphoSite	Q9HBY8.
Polymorphism databases
DMDM	28558166.
Proteomic databases
PaxDb	Q9HBY8.
PRIDE	Q9HBY8.
Protocols and materials databases
DNASU	10110.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000341458; ENSP00000340608; ENSG00000101049. ENST00000373077; ENSP00000362168; ENSG00000101049. ENST00000373092; ENSP00000362184; ENSG00000101049. ENST00000373100; ENSP00000362192; ENSG00000101049. ENST00000423407; ENSP00000392795; ENSG00000101049. ENST00000426287; ENSP00000412214; ENSG00000101049.
GeneID	10110.
KEGG	hsa:10110.
UCSC	uc002xkr.3. human.
Organism-specific databases
CTD	10110.
GeneCards	GC20P042187.
H-InvDB	HIX0080189.
HGNC	HGNC:13900. SGK2.
HPA	HPA011387.
MIM	607589. gene.
neXtProt	NX_Q9HBY8.
PharmGKB	PA37824.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233033.
HOVERGEN	HBG108317.
InParanoid	Q9HBY8.
KO	K13303.
OMA	CQGHVVL.
PhylomeDB	Q9HBY8.
Gene expression databases
ArrayExpress	Q9HBY8.
Bgee	Q9HBY8.
CleanEx	HS_SGK2.
Genevestigator	Q9HBY8.
GermOnline	ENSG00000101049. Homo sapiens.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR011009. Kinase-like_dom. 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. [Graphical view]
SMART	SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 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. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5794.
GenomeRNAi	10110.
NextBio	38243.
SOURCE	Search...

Entry information

Entry name

SGK2_HUMAN

Accession

Primary (citable) accession number: Q9HBY8
Secondary accession number(s): Q52PK5 , Q5H8Y6, Q5H8Z1, Q5TZR3, Q9UKG6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 22, 2003
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.