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P31751 (AKT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
RAC-beta serine/threonine-protein kinase

EC=2.7.11.1
Alternative name(s):
Protein kinase Akt-2
Protein kinase B beta
Short name=PKB beta
RAC-PK-beta
Gene names
Name:AKT2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length481 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificityhas been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform ofcyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI3P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI3K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Ref.10 Ref.20

One of the few specific substrates of AKT2 identified recently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsibleof the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'. Ref.10 Ref.20

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. Aminofurazans are potent AKT2 inhibitors. Ref.27 Ref.28

Subunit structure

Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CLK2, PBH2 and TRAF6. Interacts (when phosphorylated) with CLIP3, the interaction promotes cell membrane localization. Ref.7 Ref.10 Ref.13 Ref.15 Ref.20

Subcellular location

Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Note: Localizes within both nucleus and cytoplasm of proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts. By virtue of the N-terminal PH domain, is recruited to sites of the plasma membrane containing increased PI(3,4,5)P3 or PI(3,4)P2, cell membrane targeting is also facilitared by interaction with CLIP3. Ref.10 Ref.13

Tissue specificity

Expressed in all cell types so far analyzed.

Domain

Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane.

Post-translational modification

Phosphorylation on Thr-309 and Ser-474 is required for full activity.

Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT2 ubiquitination. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. Ref.6 Ref.8 Ref.12 Ref.23

O-GlcNAcylation at Thr-306 and Thr-313 inhibits activating phosphorylation at Thr-309 via disrupting the interaction between AKT and PDK1 By similarity.

Involvement in disease

Defects in AKT2 are a cause of susceptibility to breast cancer (BC). AKT2 promotes metastasis of tumor cells without affecting the latency of tumor development. With AKT3, plays also a pivotal role in the biology of glioblastoma.

Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.29 Ref.31

Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) [MIM:240900]: A disorder characterized by hypoglycemia, low insulin levels, low serum levels of ketone bodies and branched-chain amino acids, left-sided hemihypertrophy, neonatal macrosomia, reduced consciousness and hypoglycemic seizures.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.32

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.

Caution

In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specificfunctions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.

Biophysicochemical properties

Kinetic parameters:

KM=358.4 µM for ATP (for purified and in vitro activated AKT2) Ref.9

KM=3.4 µM for peptide substrate (for purified and in vitro activated AKT2)

KM=564 µM for ATP (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells)

KM=2.3 µM for peptide substrate (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells)

Ontologies

Keywords
   Biological processApoptosis
Carbohydrate metabolism
Glucose metabolism
Glycogen biosynthesis
Glycogen metabolism
Sugar transport
Translation regulation
Transport
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDiabetes mellitus
Disease mutation
Proto-oncogene
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Disulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of Ral GTPase activity

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

carbohydrate transport

Inferred from electronic annotation. Source: UniProtKB-KW

cellular protein modification process

Traceable author statement Ref.2. Source: ProtInc

cellular response to insulin stimulus

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

fat cell differentiation

Traceable author statement Ref.19. Source: UniProtKB

glucose metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

glycogen biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

insulin receptor signaling pathway

Traceable author statement Ref.19. Source: UniProtKB

intracellular protein transmembrane transport

Inferred from sequence or structural similarity. Source: UniProtKB

mammary gland epithelial cell differentiation

Traceable author statement Ref.19. Source: UniProtKB

membrane organization

Traceable author statement. Source: Reactome

negative regulation of plasma membrane long-chain fatty acid transport

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

peripheral nervous system myelin maintenance

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell motility

Inferred from mutant phenotype PubMed 17332325. Source: BHF-UCL

positive regulation of fatty acid beta-oxidation

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

positive regulation of glucose import

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

positive regulation of glucose import in response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of glucose metabolic process

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

positive regulation of glycogen biosynthetic process

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

positive regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein targeting to membrane

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of vesicle fusion

Inferred from sequence or structural similarity. Source: UniProtKB

protein localization to plasma membrane

Inferred from electronic annotation. Source: Ensembl

regulation of cell cycle arrest

Traceable author statement Ref.19. Source: UniProtKB

regulation of cell migration

Traceable author statement Ref.19. Source: UniProtKB

regulation of translation

Inferred from electronic annotation. Source: UniProtKB-KW

signal transduction

Traceable author statement Ref.19. Source: UniProtKB

   Cellular_componentcell cortex

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.12. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.9. Source: UniProtKB

kinase activity

Traceable author statement. Source: Reactome

protein serine/threonine kinase activity

Inferred from direct assay Ref.9. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 481481RAC-beta serine/threonine-protein kinase
PRO_0000085608

Regions

Domain5 – 108104PH
Domain152 – 409258Protein kinase
Domain410 – 48172AGC-kinase C-terminal
Nucleotide binding158 – 1669ATP By similarity
Region230 – 2323Inhibitor binding
Region277 – 2793Inhibitor binding
Region292 – 2932Inhibitor binding

Sites

Active site2751Proton acceptor By similarity
Binding site1811ATP By similarity
Binding site1811Inhibitor
Binding site2001Inhibitor
Binding site2321Inhibitor; via amide nitrogen
Binding site2361Inhibitor
Binding site2791Inhibitor; via carbonyl oxygen
Binding site2801Manganese
Binding site2931Inhibitor
Binding site2931Manganese
Binding site2941Inhibitor; via amide nitrogen

Amino acid modifications

Modified residue11N-acetylmethionine Ref.21
Modified residue1261Phosphoserine Ref.11
Modified residue3091Phosphothreonine; by PDPK1 Ref.6 Ref.8 Ref.12 Ref.23
Modified residue4471Phosphoserine Ref.14
Modified residue4511Phosphothreonine Ref.14
Modified residue4741Phosphoserine Ref.8 Ref.12 Ref.14
Modified residue4781Phosphoserine Ref.14
Glycosylation1281O-linked (GlcNAc) By similarity
Glycosylation1311O-linked (GlcNAc) By similarity
Glycosylation3061O-linked (GlcNAc) By similarity
Glycosylation3131O-linked (GlcNAc) By similarity
Disulfide bond60 ↔ 77 By similarity
Disulfide bond297 ↔ 311 Ref.24

Natural variations

Natural variant171E → K in HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes. Ref.32
VAR_067309
Natural variant1881I → V. Ref.30
Corresponds to variant rs55859611 [ dbSNP | Ensembl ].
VAR_040356
Natural variant2081R → K. Ref.30
Corresponds to variant rs35817154 [ dbSNP | Ensembl ].
VAR_040357
Natural variant2741R → H in NIDDM; associated with typical metabolic dyslipidemia with elevated fastin triglyceride, high VLDL triglyceride/cholesterol ratios, low HDL cholesterol levels and high small dense LDL levels; de novo lipogenesis and liver fat are also significantly elevated in this subject. Ref.29 Ref.31
VAR_067310

Experimental info

Mutagenesis3091T → A: Impairs interaction with TTC3; when associated with A-474. Ref.8 Ref.12
Mutagenesis3091T → E: Constitutively active; when associated with D-474. Ref.8 Ref.12
Mutagenesis4741S → A: Impairs interaction with TTC3; when associated with A-309. Ref.8 Ref.12
Mutagenesis4741S → D: Constitutively active; when associated with E-309. Ref.8 Ref.12
Sequence conflict478 – 4814SIRE → FREEKDLLMSLFVSLILFSD FSSLKSHSFSSNFILLSFSS LKK in AAA36585. Ref.1

Secondary structure

.................................................................................... 481
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P31751 [UniParc].

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

FASTA48155,769
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[4]"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].
Tissue: Lymph.
[5]NIEHS SNPs program
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 237-277.
[6]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, PHOSPHORYLATION AT THR-309 BY PDPK1.
[7]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MTCP1; TCL1A AND TCL1B.
[8]"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] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-309 AND SER-474, PHOSPHORYLATION AT THR-309 AND SER-474.
[9]"Kinetic mechanism of AKT/PKB enzyme family."
Zhang X., Zhang S., Yamane H., Wahl R., Ali A., Lofgren J.A., Kendall R.L.
J. Biol. Chem. 281:13949-13956(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[10]"Akt2 is implicated in skeletal muscle differentiation and specifically binds Prohibitin2/REA."
Heron-Milhavet L., Mamaeva D., Rochat A., Lamb N.J., Fernandez A.
J. Cell. Physiol. 214:158-165(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PBH2.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt."
Suizu F., Hiramuki Y., Okumura F., Matsuda M., Okumura A.J., Hirata N., Narita M., Kohno T., Yokota J., Bohgaki M., Obuse C., Hatakeyama S., Obata T., Noguchi M.
Dev. Cell 17:800-810(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY TTC3, PHOSPHORYLATION AT THR-309 AND SER-474, MUTAGENESIS OF THR-309 AND SER-474.
[13]"ClipR-59 interacts with Akt and regulates Akt cellular compartmentalization."
Ding J., Du K.
Mol. Cell. Biol. 29:1459-1471(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLIP3, SUBCELLULAR LOCATION.
[14]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447; THR-451; SER-474 AND SER-478, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[15]"The E3 ligase TRAF6 regulates Akt ubiquitination and activation."
Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.
Science 325:1134-1138(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH TRAF6.
[16]"Akt2 and Akt3 play a pivotal role in malignant gliomas."
Mure H., Matsuzaki K., Kitazato K.T., Mizobuchi Y., Kuwayama K., Kageji T., Nagahiro S.
Neuro-oncol. 12:221-232(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CANCER.
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Akt signalling in health and disease."
Hers I., Vincent E.E., Tavare J.M.
Cell. Signal. 23:1515-1527(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[19]"Akt1 and Akt2: differentiating the aktion."
Heron-Milhavet L., Khouya N., Fernandez A., Lamb N.J.
Histol. Histopathol. 26:651-662(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[20]"Ankrd2/ARPP is a novel Akt2 specific substrate and regulates myogenic differentiation upon cellular exposure to H(2)O(2)."
Cenni V., Bavelloni A., Beretti F., Tagliavini F., Manzoli L., Lattanzi G., Maraldi N.M., Cocco L., Marmiroli S.
Mol. Biol. Cell 22:2946-2956(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MUSCLE DIFFERENTIATION, INTERACTION WITH ANKRD2.
[21]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation."
Yang J., Cron P., Thompson V., Good V.M., Hess D., Hemmings B.A., Barford D.
Mol. Cell 9:1227-1240(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 146-480.
[23]"Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP."
Yang J., Cron P., Good V.M., Thompson V., Hemmings B.A., Barford D.
Nat. Struct. Biol. 9:940-944(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 146-467 IN COMPLEX WITH PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER AND MANGANESE, PHOSPHORYLATION AT THR-309.
[24]"Crystal structure of an inactive Akt2 kinase domain."
Huang X., Begley M., Morgenstern K.A., Gu Y., Rose P., Zhao H., Zhu X.
Structure 11:21-30(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 143-481, ATP-BINDING, SUBSTRATE-BINDING, DISULFIDE BOND.
[25]"Solution structure and backbone dynamics of the pleckstrin homology domain of the human protein kinase B (PKB/Akt). Interaction with inositol phosphates."
Auguin D., Barthe P., Auge-Senegas M.T., Stern M.H., Noguchi M., Roumestand C.
J. Biomol. NMR 28:137-155(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-111.
[26]"A structural comparison of inhibitor binding to PKB, PKA and PKA-PKB chimera."
Davies T.G., Verdonk M.L., Graham B., Saalau-Bethell S., Hamlett C.C., McHardy T., Collins I., Garrett M.D., Workman P., Woodhead S.J., Jhoti H., Barford D.
J. Mol. Biol. 367:882-894(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 146-467, INHIBITOR-BINDING.
[27]"Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase."
Heerding D.A., Rhodes N., Leber J.D., Clark T.J., Keenan R.M., Lafrance L.V., Li M., Safonov I.G., Takata D.T., Venslavsky J.W., Yamashita D.S., Choudhry A.E., Copeland R.A., Lai Z., Schaber M.D., Tummino P.J., Strum S.L., Wood E.R. expand/collapse author list , Duckett D.R., Eberwein D., Knick V.B., Lansing T.J., McConnell R.T., Zhang S., Minthorn E.A., Concha N.O., Warren G.L., Kumar R.
J. Med. Chem. 51:5663-5679(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 146-480, ENZYME REGULATION.
[28]"Aminofurazans as potent inhibitors of AKT kinase."
Rouse M.B., Seefeld M.A., Leber J.D., McNulty K.C., Sun L., Miller W.H., Zhang S., Minthorn E.A., Concha N.O., Choudhry A.E., Schaber M.D., Heerding D.A.
Bioorg. Med. Chem. Lett. 19:1508-1511(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 146-480, ENZYME REGULATION.
[29]"A family with severe insulin resistance and diabetes due to a mutation in AKT2."
George S., Rochford J.J., Wolfrum C., Gray S.L., Schinner S., Wilson J.C., Soos M.A., Murgatroyd P.R., Williams R.M., Acerini C.L., Dunger D.B., Barford D., Umpleby A.M., Wareham N.J., Davies H.A., Schafer A.J., Stoffel M., O'Rahilly S., Barroso I.
Science 304:1325-1328(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NIDDM HIS-274.
[30]"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] VAL-188 AND LYS-208.
[31]"Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis."
Semple R.K., Sleigh A., Murgatroyd P.R., Adams C.A., Bluck L., Jackson S., Vottero A., Kanabar D., Charlton-Menys V., Durrington P., Soos M.A., Carpenter T.A., Lomas D.J., Cochran E.K., Gorden P., O'Rahilly S., Savage D.B.
J. Clin. Invest. 119:315-322(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT NIDDM HIS-274 WITH TYPICAL METABOLIC DYSLIPIDEMIA.
[32]"An activating mutation of AKT2 and human hypoglycemia."
Hussain K., Challis B., Rocha N., Payne F., Minic M., Thompson A., Daly A., Scott C., Harris J., Smillie B.J., Savage D.B., Ramaswami U., De Lonlay P., O'Rahilly S., Barroso I., Semple R.K.
Science 334:474-474(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIHGHH LYS-17.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M77198 mRNA. Translation: AAA36585.1.
M95936 mRNA. Translation: AAA58364.1.
AK314619 mRNA. Translation: BAG37185.1.
BC032709 mRNA. Translation: AAH32709.1.
BC120994 mRNA. Translation: AAI20995.1.
AY708392 Genomic DNA. Translation: AAT97984.1.
PIRA46288.
RefSeqNP_001617.1. NM_001626.5.
UniGeneHs.631535.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GZKX-ray2.30A146-460[»]
1GZNX-ray2.50A146-480[»]
1GZOX-ray2.75A146-460[»]
1MRVX-ray2.80A143-481[»]
1MRYX-ray2.80A143-481[»]
1O6KX-ray1.70A146-481[»]
1O6LX-ray1.60A146-467[»]
1P6SNMR-A1-111[»]
2JDOX-ray1.80A146-467[»]
2JDRX-ray2.30A146-467[»]
2UW9X-ray2.10A146-467[»]
2X39X-ray1.93A146-467[»]
2XH5X-ray2.72A146-467[»]
3D0EX-ray2.00A/B146-480[»]
3E87X-ray2.30A/B146-480[»]
3E88X-ray2.50A/B146-480[»]
3E8DX-ray2.70A/B146-480[»]
DisProtDP00304.
ProteinModelPortalP31751.
SMRP31751. Positions 1-480.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106711. 35 interactions.
DIPDIP-32583N.
IntActP31751. 20 interactions.
MINTMINT-87790.
STRING9606.ENSP00000375892.

Chemistry

BindingDBP31751.
ChEMBLCHEMBL2111353.
GuidetoPHARMACOLOGY1480.

PTM databases

PhosphoSiteP31751.

Polymorphism databases

DMDM1170703.

Proteomic databases

PaxDbP31751.
PRIDEP31751.

Protocols and materials databases

DNASU208.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000392038; ENSP00000375892; ENSG00000105221.
ENST00000424901; ENSP00000399532; ENSG00000105221.
GeneID208.
KEGGhsa:208.
UCSCuc002one.3. human.

Organism-specific databases

CTD208.
GeneCardsGC19M040736.
HGNCHGNC:392. AKT2.
HPACAB004204.
MIM125853. phenotype.
164731. gene.
240900. phenotype.
neXtProtNX_P31751.
Orphanet79085. Familial partial lipodystrophy due to AKT2 mutations.
293964. Hypoinsulinemic hypoglycemia and body hemihypertrophy.
PharmGKBPA24685.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidP31751.
KOK04456.
OrthoDBEOG7Q5HCW.
PhylomeDBP31751.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.
REACT_1123. Inhibition of HSL.
REACT_116125. Disease.
REACT_578. Apoptosis.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP31751.

Gene expression databases

ArrayExpressP31751.
BgeeP31751.
CleanExHS_AKT2.
GenevestigatorP31751.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAKT2. human.
EvolutionaryTraceP31751.
GeneWikiAKT2.
GenomeRNAi208.
NextBio836.
PROP31751.
SOURCESearch...

Entry information

Entry nameAKT2_HUMAN
AccessionPrimary (citable) accession number: P31751
Secondary accession number(s): B2RBD8 expand/collapse secondary AC list , Q05BV0, Q0VAN1, Q68GC0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 155 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 19

Human chromosome 19: entries, gene names and cross-references to MIM