Mus musculus Protein: Akt1
InnateDB Protein IDBP-174625.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Akt1
Protein Name thymoma viral proto-oncogene 1
Synonyms Akt; PKB; PKB/Akt; PKBalpha; Rac;
Species Mus musculus
Ensembl Protein ENSMUSP00000001780
InnateDB Gene IDBG-174623 (Akt1)
Protein Structure
UniProt Annotation
Function AKT1 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. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr- 117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (By similarity). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (By similarity). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (By similarity). {ECO:0000250}.AKT1-specific substrates have been recently identified, including palladin (PALLD), which phosphorylation modulates cytoskeletal organization and cell motility; prohibitin (PHB), playing an important role in cell metabolism and proliferation; and CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation. {ECO:0000269PubMed:10454575, ECO:0000269PubMed:11282895, ECO:0000269PubMed:11579209, ECO:0000269PubMed:11994271, ECO:0000269PubMed:12783884, ECO:0000269PubMed:18288188, ECO:0000269PubMed:19778506, ECO:0000269PubMed:20333297, ECO:0000269PubMed:22057101, ECO:0000269PubMed:9415393}.
Subcellular Localization Cytoplasm. Nucleus. Cell membrane {ECO:0000250}. Note=Nucleus after activation by integrin-linked protein kinase 1 (ILK1) (By similarity). Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus. {ECO:0000250}.
Disease Associations
Tissue Specificity Widely expressed. Low levels found in liver with slightly higher levels present in thymus and testis. {ECO:0000269PubMed:8437858}.
Number of Interactions This gene and/or its encoded proteins are associated with 86 experimentally validated interaction(s) in this database.
They are also associated with 254 interaction(s) predicted by orthology.
Experimentally validated
Total 86 [view]
Protein-Protein 86 [view]
Protein-DNA 0
Protein-RNA 0
Predicted by orthology
Total 254 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004712 protein serine/threonine/tyrosine kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005080 protein kinase C binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding
GO:0016301 kinase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0030235 nitric-oxide synthase regulator activity
GO:0042802 identical protein binding
GO:0043325 phosphatidylinositol-3,4-bisphosphate binding
GO:0071889 14-3-3 protein binding
Biological Process
GO:0000060 protein import into nucleus, translocation
GO:0001649 osteoblast differentiation
GO:0001893 maternal placenta development
GO:0001934 positive regulation of protein phosphorylation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0005977 glycogen metabolic process
GO:0005978 glycogen biosynthetic process
GO:0005979 regulation of glycogen biosynthetic process
GO:0006006 glucose metabolic process
GO:0006412 translation
GO:0006417 regulation of translation
GO:0006468 protein phosphorylation
GO:0006469 negative regulation of protein kinase activity
GO:0006924 activation-induced cell death of T cells
GO:0006954 inflammatory response
GO:0007010 cytoskeleton organization
GO:0007165 signal transduction
GO:0007281 germ cell development
GO:0007568 aging
GO:0008286 insulin receptor signaling pathway
GO:0008637 apoptotic mitochondrial changes
GO:0009725 response to hormone
GO:0010507 negative regulation of autophagy
GO:0010748 negative regulation of plasma membrane long-chain fatty acid transport
GO:0010765 positive regulation of sodium ion transport
GO:0010907 positive regulation of glucose metabolic process
GO:0010951 negative regulation of endopeptidase activity
GO:0010975 regulation of neuron projection development
GO:0015758 glucose transport
GO:0016310 phosphorylation
GO:0016567 protein ubiquitination
GO:0018105 peptidyl-serine phosphorylation
GO:0030030 cell projection organization
GO:0030163 protein catabolic process
GO:0030212 hyaluronan metabolic process
GO:0030307 positive regulation of cell growth
GO:0030334 regulation of cell migration
GO:0031018 endocrine pancreas development
GO:0031659 positive regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0031999 negative regulation of fatty acid beta-oxidation
GO:0032094 response to food
GO:0032270 positive regulation of cellular protein metabolic process
GO:0032287 peripheral nervous system myelin maintenance
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032869 cellular response to insulin stimulus
GO:0032880 regulation of protein localization
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0034405 response to fluid shear stress
GO:0035556 intracellular signal transduction
GO:0042593 glucose homeostasis
GO:0042640 anagen
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043491 protein kinase B signaling
GO:0043536 positive regulation of blood vessel endothelial cell migration
GO:0045087 innate immune response (InnateDB)
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045600 positive regulation of fat cell differentiation
GO:0045725 positive regulation of glycogen biosynthetic process
GO:0045792 negative regulation of cell size
GO:0045861 negative regulation of proteolysis
GO:0045907 positive regulation of vasoconstriction
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046326 positive regulation of glucose import
GO:0046329 negative regulation of JNK cascade
GO:0046889 positive regulation of lipid biosynthetic process
GO:0048009 insulin-like growth factor receptor signaling pathway
GO:0051000 positive regulation of nitric-oxide synthase activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051146 striated muscle cell differentiation
GO:0060709 glycogen cell differentiation involved in embryonic placenta development
GO:0060716 labyrinthine layer blood vessel development
GO:0070141 response to UV-A
GO:0071260 cellular response to mechanical stimulus
GO:0071363 cellular response to growth factor stimulus
GO:0071364 cellular response to epidermal growth factor stimulus
GO:0071407 cellular response to organic cyclic compound
GO:0071456 cellular response to hypoxia
GO:0090004 positive regulation of establishment of protein localization to plasma membrane
GO:0090201 negative regulation of release of cytochrome c from mitochondria
GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus
GO:0097194 execution phase of apoptosis
GO:1901653 cellular response to peptide
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005819 spindle
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005911 cell-cell junction
GO:0015630 microtubule cytoskeleton
GO:0036064 ciliary basal body
Protein Structure and Domains
PDB ID MGI:87986
InterPro IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001849 Pleckstrin homology domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR017892 Protein kinase, C-terminal
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF00069
Post-translational Modifications
SwissProt P31750
PhosphoSite PhosphoSite-P31750
UniProt Splice Variant
Entrez Gene 11651
UniGene Mm.6645
RefSeq NP_033782
MGI Symbol Akt1
EMBL AC124373 AF534134 AK154936 BC066018 CH466549 KF836746 M94335 X65687
GenPept AAA18254 AAH66018 AAN04036 AHA61678 BAE32937 CAA46620 EDL18586