This gene is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains. 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 can... See more...

Aliases for AKT2 Gene

Aliases for AKT2 Gene

  • AKT Serine/Threonine Kinase 2 2 3 5
  • V-Akt Murine Thymoma Viral Oncogene Homolog 2 2 3
  • RAC-Beta Serine/Threonine-Protein Kinase 3 4
  • Protein Kinase B Beta 3 4
  • Protein Kinase Akt-2 3 4
  • RAC-PK-Beta 3 4
  • EC 2.7.11.1 4 54
  • PKB Beta 3 4
  • Putative V-Akt Murine Thymoma Viral Oncoprotein 2 3
  • Murine Thymoma Viral (V-Akt) Homolog-2 3
  • Rac Protein Kinase Beta 3
  • EC 2.7.11 54
  • RAC-BETA 3
  • PKBBETA 3
  • HIHGHH 3
  • PRKBB 3
  • PKBB 3

External Ids for AKT2 Gene

Previous GeneCards Identifiers for AKT2 Gene

  • GC19M041377
  • GC19M041129
  • GC19M045414
  • GC19M045431
  • GC19M045430
  • GC19M040736
  • GC19M037171

Summaries for AKT2 Gene

Entrez Gene Summary for AKT2 Gene

  • This gene is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains. 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. The encoded protein is a general protein kinase capable of phophorylating several known proteins. [provided by RefSeq, Jul 2008]

CIViC Summary for AKT2 Gene

GeneCards Summary for AKT2 Gene

AKT2 (AKT Serine/Threonine Kinase 2) is a Protein Coding gene. Diseases associated with AKT2 include Hypoinsulinemic Hypoglycemia With Hemihypertrophy and Diabetes Mellitus, Noninsulin-Dependent. Among its related pathways are Vesicle-mediated transport and VEGF Signaling Pathway. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is AKT1.

UniProtKB/Swiss-Prot Summary for AKT2 Gene

  • 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 specificity has 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 of cyclic 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 PI(3)P-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 (PI(3)K) 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.
  • 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 responsible of 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'.

Tocris Summary for AKT2 Gene

  • Akt (Protein kinase B, PKB) is a serine/threonine kinase that plays a key in regulating cell survival, insulin signaling, angiogenesis and tumor formation. Akt is a downstream mediator of the PI 3-K pathway, which results in the recruitment of Akt to the plasma membrane.

Gene Wiki entry for AKT2 Gene

Additional gene information for AKT2 Gene

No data available for PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AKT2 Gene

Genomics for AKT2 Gene

GeneHancer (GH) Regulatory Elements for AKT2 Gene

Promoters and enhancers for AKT2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AKT2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the AKT2 gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • CREB
  • deltaCREB
  • p300
  • STAT3

Genomic Locations for AKT2 Gene

Genomic Locations for AKT2 Gene
chr19:40,230,317-40,285,536
(GRCh38/hg38)
Size:
55,220 bases
Orientation:
Minus strand
chr19:40,736,224-40,791,443
(GRCh37/hg19)
Size:
55,220 bases
Orientation:
Minus strand

Genomic View for AKT2 Gene

Genes around AKT2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AKT2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AKT2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AKT2 Gene

Proteins for AKT2 Gene

  • Protein details for AKT2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P31751-AKT2_HUMAN
    Recommended name:
    RAC-beta serine/threonine-protein kinase
    Protein Accession:
    P31751
    Secondary Accessions:
    • B2RBD8
    • Q05BV0
    • Q0VAN0
    • Q0VAN1
    • Q68GC0

    Protein attributes for AKT2 Gene

    Size:
    481 amino acids
    Molecular mass:
    55769 Da
    Quaternary structure:
    • Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). 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 (PubMed:19139280). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529).

    Three dimensional structures from OCA and Proteopedia for AKT2 Gene

    Alternative splice isoforms for AKT2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AKT2 Gene

Selected DME Specific Peptides for AKT2 Gene

P31751:
  • CQLMKTERP
  • TPPDRYD
  • YYAMKIL
  • AEIVSAL
  • GTPEYLAPE
  • RAVDWWGLGV
  • DGSFIGYKE
  • HPFLTAL
  • HFPQFSYSAS
  • NGGELFFHL
  • LFELILME
  • IKITDFGL
  • RFYGAEI
  • KEVIIAKDEVAHT
  • PLNNFSVA
  • NLMLDKD
  • HPFLTALKY
  • LQWTTVIERTF
  • YLAPEVL
  • RDIKLEN
  • PPFKPQVTSE
  • GVVMYEM
  • PEAKSLL
  • YLKLLGKGTFGKVILV
  • YAMKILRK
  • IKITDFG
  • LDKDGHIK
  • GLLKKDPKQRLGGG
  • LFFHLSRERVF
  • DFGLCKE
  • DTRYFDDEFTAQSIT
  • DRLCFVM
  • KRGEYIK

Post-translational modifications for AKT2 Gene

  • 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.
  • O-GlcNAcylation at Thr-306 and Thr-313 inhibits activating phosphorylation at Thr-309 via disrupting the interaction between AKT and PDK1.
  • Glycosylation at Ser128, Ser131, Thr306, and Thr313
  • Ubiquitination at Lys30 and Lys378
  • Modification sites at PhosphoSitePlus

Antibody Products

Domains & Families for AKT2 Gene

Gene Families for AKT2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for AKT2 Gene

GenScript: Design optimal peptide antigens:
  • RAC-PK-beta (AKT2_HUMAN)
  • cDNA FLJ31217 fis, clone KIDNE2004095, highly similar to RAC-beta serine/threonine-protein kinase (EC 2.7.11.1) (B3KP61_HUMAN)
  • cDNA FLJ58721, highly similar to RAC-beta serine/threonine-protein kinase (EC2.7.11.1) (B7Z8Z9_HUMAN)
  • AKT2 protein (Q05BV0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P31751

UniProtKB/Swiss-Prot:

AKT2_HUMAN :
  • 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.
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
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.
Family:
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
genes like me logo Genes that share domains with AKT2: view

Function for AKT2 Gene

Molecular function for AKT2 Gene

UniProtKB/Swiss-Prot 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 specificity has 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 of cyclic 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 PI(3)P-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 (PI(3)K) 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.
UniProtKB/Swiss-Prot Function:
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 responsible of 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'.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;.
UniProtKB/Swiss-Prot EnzymeRegulation:
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.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=358.4 uM for ATP (for purified and in vitro activated AKT2) {ECO:0000269 PubMed:16540465}; KM=3.4 uM for peptide substrate (for purified and in vitro activated AKT2) {ECO:0000269 PubMed:16540465}; KM=564 uM for ATP (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells) {ECO:0000269 PubMed:16540465}; KM=2.3 uM for peptide substrate (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells) {ECO:0000269 PubMed:16540465};
GENATLAS Biochemistry:
V-akt murine thymoma viral oncogen homolog 2,general mediator of cell survival induced by insulin growth factor 1,AKT2 and others,activated by phosphatidylinositol 3-

Enzyme Numbers (IUBMB) for AKT2 Gene

Phenotypes From GWAS Catalog for AKT2 Gene

Gene Ontology (GO) - Molecular Function for AKT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity TAS,IBA 21432781
GO:0005515 protein binding IPI 10490823
GO:0005524 ATP binding IDA 16540465
GO:0016301 kinase activity IEA --
genes like me logo Genes that share ontologies with AKT2: view
genes like me logo Genes that share phenotypes with AKT2: view

Human Phenotype Ontology for AKT2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for AKT2 Gene

MGI Knock Outs for AKT2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AKT2

Clone Products

  • Addgene plasmids for AKT2

No data available for Transcription Factor Targets and HOMER Transcription for AKT2 Gene

Localization for AKT2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AKT2 Gene

Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Early endosome. 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. Colocalizes with WDFY2 in early endosomes (By similarity). {ECO:0000250 UniProtKB:Q60823}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AKT2 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 4
endosome 3
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleus (3)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for AKT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS 21432781
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA --
genes like me logo Genes that share ontologies with AKT2: view

Pathways & Interactions for AKT2 Gene

PathCards logo

SuperPathways for AKT2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Regulation of lipid metabolism Insulin signaling-generic cascades
3 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
4 Endometrial cancer
5 Development HGF signaling pathway
genes like me logo Genes that share pathways with AKT2: view

Pathways by source for AKT2 Gene

35 Qiagen pathways for AKT2 Gene
  • Akt Signaling
  • AMPK Enzyme Complex Pathway
  • cAMP Pathway
  • CD28 Signaling in T-Helper Cell
  • CTLA4 Signaling
2 Cell Signaling Technology pathways for AKT2 Gene

Gene Ontology (GO) - Biological Process for AKT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001934 positive regulation of protein phosphorylation ISS --
GO:0005975 carbohydrate metabolic process IEA --
GO:0005977 glycogen metabolic process IEA --
GO:0005978 glycogen biosynthetic process IEA --
GO:0006006 glucose metabolic process IEA --
genes like me logo Genes that share ontologies with AKT2: view

Drugs & Compounds for AKT2 Gene

(74) Drugs for AKT2 Gene - From: DrugBank, ClinicalTrials, ApexBio, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Everolimus Approved Pharma inhibitor, Biomarker mTOR inhibitor, mTOR Inhibitors, Kinase Inhibitors, Mammalian target of rapamycin (mTOR) inhibitors 1923
Paclitaxel Approved, Vet_approved Pharma Tubulin and Bcl2 inhibitor, Taxanes 3454
Tyrosine Approved, Investigational Nutra 938
Anastrozole Approved, Investigational