AKT2

V-akt murine thymoma viral oncogene homolog 2

PDB rendering based on 1gzk.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1GZK, 1GZN, 1GZO, 1MRV, 1MRY, 1O6K, 1O6L, 1P6S, 2JDO, 2JDR, 2UW9, 2X39, 2XH5, 3D0E, 3E87, 3E88, 3E8D

Identifiers

Symbols

AKT2 ; HIHGHH; PKBB; PKBBETA; PRKBB; RAC-BETA

External IDs

OMIM: 164731 MGI: 104874 HomoloGene: 48773 ChEMBL: 2431 GeneCards: AKT2 Gene

EC number

2.7.11.1

Gene ontology
Molecular function	• protein serine/threonine kinase activity • protein kinase C binding • protein binding • ATP binding • kinase activity
Cellular component	• nucleus • nucleoplasm • cytosol • plasma membrane • cell cortex • ruffle membrane • insulin-responsive compartment
Biological process	• positive regulation of protein phosphorylation • glycogen biosynthetic process • glucose metabolic process • regulation of translation • cellular protein modification process • protein phosphorylation • response to osmotic stress • signal transduction • insulin receptor signaling pathway • carbohydrate transport • positive regulation of signal transduction • negative regulation of plasma membrane long-chain fatty acid transport • positive regulation of glucose metabolic process • response to muscle activity • regulation of cell migration • positive regulation of cell migration • positive regulation of vesicle fusion • response to nutrient levels • positive regulation of fatty acid beta-oxidation • peripheral nervous system myelin maintenance • cellular response to insulin stimulus • negative regulation of RNA splicing • positive regulation of peptidyl-serine phosphorylation • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • protein kinase B signaling • positive regulation of nitric oxide biosynthetic process • fat cell differentiation • positive regulation of glycogen biosynthetic process • positive regulation of transcription from RNA polymerase II promoter • positive regulation of glucose import • positive regulation of positive chemotaxis • mammary gland epithelial cell differentiation • membrane organization • intracellular protein transmembrane transport • regulation of cell cycle arrest • cellular response to organic cyclic compound • protein localization to plasma membrane • positive regulation of protein targeting to membrane • activation of GTPase activity • positive regulation of cell motility • positive regulation of glucose import in response to insulin stimulus
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

208

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
40.23 – 40.29 Mb

Chr 7:
27.59 – 27.64 Mb

PubMed search

RAC-beta serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT2 gene.^[1]

Function

This gene is a putative oncogene encoding a protein belonging to the AKT subfamily of serine/threonine kinases that contain SH2-like (Src homology 2-like) domains. The encoded protein is a general protein kinase capable of phosphorylating several known proteins.^[2]

Clinical significance

The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers.^[2]

Mice lacking Akt2 have a normal body mass, but display a profound diabetic phenotype, indicating that Akt2 plays a key role in signal transduction downstream of the insulin receptor. Mice lacking Akt2 show worse outcome in breast cancer initaited by the large T antigen as well as the neu oncogene.^[3]

Interactions

AKT2 has been shown to interact with:

References

↑ Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, Tsichlis PN, Testa JR (November 1992). "AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas". Proc Natl Acad Sci U S A 89 (19): 9267–71. doi:10.1073/pnas.89.19.9267. PMC 50107. PMID 1409633.
1 2 "Entrez Gene: AKT2 v-akt murine thymoma viral oncogene homolog 2".
↑ Heron-Milhavet L, Khouya N, Fernandez A, Lamb NJ (2011). "Akt1 and Akt2: differentiating the aktion". Histol. Histopathol. 26 (5): 651–62. PMID 21432781.
↑ Mitsuuchi Y, Johnson SW, Sonoda G, Tanno S, Golemis EA, Testa JR (September 1999). "Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2". Oncogene 18 (35): 4891–8. doi:10.1038/sj.onc.1203080. PMID 10490823.
↑ Yuan ZQ, Feldman RI, Sun M, Olashaw NE, Coppola D, Sussman GE, Shelley SA, Nicosia SV, Cheng JQ (August 2002). "Inhibition of JNK by cellular stress- and tumor necrosis factor alpha-induced AKT2 through activation of the NF kappa B pathway in human epithelial Cells". J. Biol. Chem. 277 (33): 29973–82. doi:10.1074/jbc.M203636200. PMID 12048203.
↑ Figueroa C, Tarras S, Taylor J, Vojtek AB (November 2003). "Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex". J. Biol. Chem. 278 (48): 47922–7. doi:10.1074/jbc.M307357200. PMID 14504284.
↑ Laine J, Künstle G, Obata T, Noguchi M (February 2002). "Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family". J. Biol. Chem. 277 (5): 3743–51. doi:10.1074/jbc.M107069200. PMID 11707444.
↑ Laine J, Künstle G, Obata T, Sha M, Noguchi M (August 2000). "The protooncogene TCL1 is an Akt kinase coactivator". Mol. Cell 6 (2): 395–407. doi:10.1016/S1097-2765(00)00039-3. PMID 10983986.

Jones PF, Jakubowicz T, Hemmings BA (1992). "Molecular cloning of a second form of rac protein kinase.". Cell Regul. 2 (12): 1001–9. doi:10.1091/mbc.2.12.1001. PMC 361900. PMID 1801921.
Staal SP (1987). "Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma.". Proc. Natl. Acad. Sci. U.S.A. 84 (14): 5034–7. doi:10.1073/pnas.84.14.5034. PMC 305241. PMID 3037531.
Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, Testa JR (1996). "Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA.". Proc. Natl. Acad. Sci. U.S.A. 93 (8): 3636–41. doi:10.1073/pnas.93.8.3636. PMC 39663. PMID 8622988.
Meier R, Alessi DR, Cron P, Andjelković M, Hemmings BA (1997). "Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta.". J. Biol. Chem. 272 (48): 30491–7. doi:10.1074/jbc.272.48.30491. PMID 9374542.
Borgatti P, Zauli G, Colamussi ML, Gibellini D, Previati M, Cantley LL, Capitani S (1998). "Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells.". Eur. J. Immunol. 27 (11): 2805–11. doi:10.1002/eji.1830271110. PMID 9394803.
Walker KS, Deak M, Paterson A, Hudson K, Cohen P, Alessi DR (1998). "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.". Biochem. J. 331. ( Pt 1): 299–308. PMC 1219352. PMID 9512493.
Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J, Lannigan DA (1998). "pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167.". Mol. Cell. Biol. 18 (4): 1978–84. PMC 121427. PMID 9528769.
Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S (1998). "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase.". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11211–6. doi:10.1073/pnas.95.19.11211. PMC 21621. PMID 9736715.
Mitsuuchi Y, Johnson SW, Sonoda G, Tanno S, Golemis EA, Testa JR (1999). "Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2.". Oncogene 18 (35): 4891–8. doi:10.1038/sj.onc.1203080. PMID 10490823.
Masure S, Haefner B, Wesselink JJ, Hoefnagel E, Mortier E, Verhasselt P, Tuytelaars A, Gordon R, Richardson A (1999). "Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3.". Eur. J. Biochem. 265 (1): 353–60. doi:10.1046/j.1432-1327.1999.00774.x. PMID 10491192.
Meucci O, Fatatis A, Simen AA, Miller RJ (2000). "Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival.". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 8075–80. doi:10.1073/pnas.090017497. PMC 16672. PMID 10869418.
Laine J, Künstle G, Obata T, Sha M, Noguchi M (2000). "The protooncogene TCL1 is an Akt kinase coactivator.". Mol. Cell 6 (2): 395–407. doi:10.1016/S1097-2765(00)00039-3. PMID 10983986.
Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H (2001). "Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance.". J. Biol. Chem. 276 (13): 9817–24. doi:10.1074/jbc.M010840200. PMID 11139588.
Zauli G, Milani D, Mirandola P, Mazzoni M, Secchiero P, Miscia S, Capitani S (2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway.". FASEB J. 15 (2): 483–91. doi:10.1096/fj.00-0354com. PMID 11156964.
Kapasi AA, Fan S, Singhal PC (2001). "Role of 14-3-3epsilon, c-Myc/Max, and Akt phosphorylation in HIV-1 gp 120-induced mesangial cell proliferation.". Am. J. Physiol. Renal Physiol. 280 (2): F333–42. PMID 11208609.
Matsumoto M, Ogawa W, Hino Y, Furukawa K, Ono Y, Takahashi M, Ohba M, Kuroki T, Kasuga M (2001). "Inhibition of insulin-induced activation of Akt by a kinase-deficient mutant of the epsilon isozyme of protein kinase C.". J. Biol. Chem. 276 (17): 14400–6. doi:10.1074/jbc.M011093200. PMID 11278835.
Brownawell AM, Kops GJ, Macara IG, Burgering BM (2001). "Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX.". Mol. Cell. Biol. 21 (10): 3534–46. doi:10.1128/MCB.21.10.3534-3546.2001. PMC 100275. PMID 11313479.
Clark DE, Poteet-Smith CE, Smith JA, Lannigan DA (2001). "Rsk2 allosterically activates estrogen receptor alpha by docking to the hormone-binding domain.". EMBO J. 20 (13): 3484–94. doi:10.1093/emboj/20.13.3484. PMC 125527. PMID 11432835.
Chen R, Kim O, Yang J, Sato K, Eisenmann KM, McCarthy J, Chen H, Qiu Y (2001). "Regulation of Akt/PKB activation by tyrosine phosphorylation.". J. Biol. Chem. 276 (34): 31858–62. doi:10.1074/jbc.C100271200. PMID 11445557.

PDB gallery

1gzk: MOLECULAR MECHANISM FOR THE REGULATION OF PROTEIN KINASE B/ AKT BY HYDROPHOBIC MOTIF PHOSPHORYLATION

1gzn: STRUCTURE OF PKB KINASE DOMAIN

1gzo: STRUCTURE OF PROTEIN KINASE B UNPHOSPHORYLATED

1mrv: crystal structure of an inactive Akt2 kinase domain

1mry: crystal structure of an inactive akt2 kinase domain

1o6k: STRUCTURE OF ACTIVATED FORM OF PKB KINASE DOMAIN S474D WITH GSK3 PEPTIDE AND AMP-PNP

1o6l: CRYSTAL STRUCTURE OF AN ACTIVATED AKT/PROTEIN KINASE B (PKB-PIF CHIMERA) TERNARY COMPLEX WITH AMP-PNP AND GSK3 PEPTIDE

1p6s: Solution Structure of the Pleckstrin Homology Domain of Human Protein Kinase B beta (Pkb/Akt)

2jdo: STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY) ETHYLAMINO)ETHYL) AMIDE

2jdr: STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH THE INHIBITOR A-443654

2uw9: STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH 4-(4-CHLORO-PHENYL)-4-(4-(1H-PYRAZOL-4-YL)-PHENYL)-PIPERIDINE

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

(3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)) (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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AKT2

Function

Clinical significance

Interactions

References

Further reading