RAC-beta serine/threonine-protein kinase

Names and origin

Protein names

Recommended name:
    RAC-beta serine/threonine-protein kinase
    EC=2.7.11.1
Alternative name(s):
    RAC-PK-beta
    Protein kinase Akt-2
    Protein kinase B, beta
      Short name=PKB beta

Gene names

Name:

AKT2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	481 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	General protein kinase capable of phosphorylating several known proteins.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser-474), need to be phosphorylated for its full activation.
Subunit structure	Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B.
Tissue specificity	In all human cell types so far analyzed.
Involvement in disease	Alterations of AKT2 may contribute to the pathogenesis of ovarian carcinomas.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 PH domain. Contains 1 protein kinase domain.

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Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein modification process Ref.2 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct
CDC37	Q16543	1	EBI-296058,EBI-295634
GSK3B	P49841	1	EBI-296058,EBI-373586
SETDB1	Q15047	1	EBI-296058,EBI-79691
SH3RF1	Q7Z6J0	1	EBI-296058,EBI-1374106

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 481

481

RAC-beta serine/threonine-protein kinase

Regions

Domain

5 – 108

104

PH

Domain

152 – 409

258

Protein kinase

Domain

410 – 481

72

AGC-kinase C-terminal

Nucleotide binding

158 – 166

9

ATP By similarity

Sites

Active site

275

1

Proton acceptor By similarity

Binding site

181

1

ATP By similarity

Amino acid modifications

Modified residue

309

1

Phosphothreonine; by PDPK1

Modified residue

474

1

Phosphoserine

Natural variations

Natural variant

1

Natural variant

1

Experimental info

Mutagenesis

309

1

T → E: Constitutively active; when associated with D-474

Mutagenesis

474

1

S → D: Constitutively active; when associated with E-309

Sequence conflict

478 – 481

4

SIRE → FREEKDLLMSLFVSLILFSD FSSLKSHSFSSNFILLSFSS LKK in AAA36585. Ref.1

Secondary structure

1

.

481

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P31751-1 [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: B18C87A7246BFB24
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FASTA

481

55,769

        10         20         30         40         50         60 
MNEVSVIKEG WLHKRGEYIK TWRPRYFLLK SDGSFIGYKE RPEAPDQTLP PLNNFSVAEC 

        70         80         90        100        110        120 
QLMKTERPRP NTFVIRCLQW TTVIERTFHV DSPDEREEWM RAIQMVANSL KQRAPGEDPM 

       130        140        150        160        170        180 
DYKCGSPSDS STTEEMEVAV SKARAKVTMN DFDYLKLLGK GTFGKVILVR EKATGRYYAM 

       190        200        210        220        230        240 
KILRKEVIIA KDEVAHTVTE SRVLQNTRHP FLTALKYAFQ THDRLCFVME YANGGELFFH 

       250        260        270        280        290        300 
LSRERVFTEE RARFYGAEIV SALEYLHSRD VVYRDIKLEN LMLDKDGHIK ITDFGLCKEG 

       310        320        330        340        350        360 
ISDGATMKTF CGTPEYLAPE VLEDNDYGRA VDWWGLGVVM YEMMCGRLPF YNQDHERLFE 

       370        380        390        400        410        420 
LILMEEIRFP RTLSPEAKSL LAGLLKKDPK QRLGGGPSDA KEVMEHRFFL SINWQDVVQK 

       430        440        450        460        470        480 
KLLPPFKPQV TSEVDTRYFD DEFTAQSITI TPPDRYDSLG LLELDQRTHF PQFSYSASIR 


E

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a second form of rac protein kinase." Jones P.F., Jakubowicz T., Hemmings B.A. Cell Regul. 2:1001-1009(1991) [PubMed: 1801921] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Epithelium.
[2]	"AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas." Cheng J.Q., Godwin A.K., Bellacosa A., Taguchi T., Franke T.F., Hamilton T.C., Tsichlis P.N., Testa J.R. Proc. Natl. Acad. Sci. U.S.A. 89:9267-9271(1992) [PubMed: 1409633] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 237-277.
[5]	"Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha." Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R. Biochem. J. 331:299-308(1998) [PubMed: 9512493] [Abstract] Cited for: CHARACTERIZATION, PHOSPHORYLATION AT THR-309 BY PDPK1.
[6]	"The protooncogene TCL1 is an Akt kinase coactivator." Laine J., Kuenstle G., Obata T., Sha M., Noguchi M. Mol. Cell 6:395-407(2000) [PubMed: 10983986] [Abstract] Cited for: INTERACTION WITH MTCP1; TCL1A AND TCL1B.
[7]	"Activation of a GST-tagged AKT2/PKBbeta." Baer K., Lisinski I., Gompert M., Stuhlmann D., Schmolz K., Klein H.W., Al-Hasani H. Biochim. Biophys. Acta 1725:340-347(2005) [PubMed: 15890450] [Abstract] Cited for: MUTAGENESIS OF THR-309 AND SER-474, PHOSPHORYLATION AT THR-309 AND SER-474.
[8]	"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. Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-188 AND LYS-208.
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Cross-references

Sequence databases

M77198 mRNA. Translation: AAA36585.1.
M95936 mRNA. Translation: AAA58364.1.
BC120994 mRNA. Translation: AAI20995.1.
AY708392 Genomic DNA. Translation: AAT97984.1.

PIR

A46288.

RefSeq

NP_001617.1.

UniGene

Hs.631535

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GZK	X-ray	2.30	A	146-460	[»]
1GZN	X-ray	2.50	A	146-480	[»]
1GZO	X-ray	2.75	A	146-460	[»]
1MRV	X-ray	2.80	A	143-481	[»]
1MRY	X-ray	2.80	A	143-481	[»]
1O6K	X-ray	1.70	A	146-481	[»]
1O6L	X-ray	1.60	A	146-467	[»]
1P6S	NMR	-	A	1-111	[»]
2UW9	X-ray	2.10	A	146-477	[»]