The AKT1 gene and its putative association with human ageing

Cell Types

Aortic endothelial, Dermal microvascular endothelial, Umbilical vein endothelial

Cell Lines

Primary cell

Cancer Cell?

No

Method

Overexpression

Type of senescence

Oncogene-induced

Senescence Effect

Induces

Primary Reference

Skeen et al. (2006) Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent manner. Cancer Cell 10(4)269-80 (PubMed)

HGNC symbol

AKT1

Aliases

AKT; PKB; PRKBA; RAC; RAC-alpha

Common name

AKT serine/threonine kinase 1

Entrez Id

207

Description

This gene encodes one of the three members of the human AKT serine-threonine protein kinase family which are often referred to as protein kinase B alpha, beta, and gamma. These highly similar AKT proteins all have an N-terminal pleckstrin homology domain, a serine/threonine-specific kinase domain and a C-terminal regulatory domain. These proteins are phosphorylated by phosphoinositide 3-kinase (PI3K). AKT/PI3K forms a key component of many signalling pathways that involve the binding of membrane-bound ligands such as receptor tyrosine kinases, G-protein coupled receptors, and integrin-linked kinase. These AKT proteins therefore regulate a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. AKT proteins are recruited to the cell membrane by phosphatidylinositol 3,4,5-trisphosphate (PIP3) after phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) by PI3K. Subsequent phosphorylation of both threonine residue 308 and serine residue 473 is required for full activation of the AKT1 protein encoded by this gene. Phosphorylation of additional residues also occurs, for example, in response to insulin growth factor-1 and epidermal growth factor. Protein phosphatases act as negative regulators of AKT proteins by dephosphorylating AKT or PIP3. The PI3K/AKT signalling pathway is crucial for tumor cell survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating AKT1 which then phosphorylates and inactivates components of the apoptotic machinery. AKT proteins also participate in the mammalian target of rapamycin (mTOR) signalling pathway which controls the assembly of the eukaryotic translation initiation factor 4F (eIF4E) complex and this pathway, in addition to responding to extracellular signals from growth factors and cytokines, is disregulated in many cancers. Mutations in this gene are associated with multiple types of cancer and excessive tissue growth including Proteus syndrome and Cowden syndrome 6, and breast, colorectal, and ovarian cancers. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2020].

Gene Ontology

Process:

GO:10628; positive regulation of gene expression
GO:6468; protein phosphorylation
GO:16310; phosphorylation
GO:43066; negative regulation of apoptotic process
GO:6915; apoptotic process
GO:5975; carbohydrate metabolic process
GO:6417; regulation of translation
GO:7165; signal transduction
GO:30154; cell differentiation
GO:5977; glycogen metabolic process
GO:7399; nervous system development
GO:18105; peptidyl-serine phosphorylation
GO:8643; carbohydrate transport
GO:8284; positive regulation of cell population proliferation
GO:43491; protein kinase B signaling
GO:5978; glycogen biosynthetic process
GO:46777; protein autophosphorylation
GO:42981; regulation of apoptotic process
GO:35556; intracellular signal transduction
GO:6006; glucose metabolic process
GO:33138; positive regulation of peptidyl-serine phosphorylation
GO:30334; regulation of cell migration
GO:71356; cellular response to tumor necrosis factor
GO:60416; response to growth hormone
GO:1990418; response to insulin-like growth factor stimulus
GO:6606; protein import into nucleus
GO:1901796; regulation of signal transduction by p53 class mediator
GO:7186; G protein-coupled receptor signaling pathway
GO:45746; negative regulation of Notch signaling pathway
GO:10595; positive regulation of endothelial cell migration
GO:14065; phosphatidylinositol 3-kinase signaling
GO:7173; epidermal growth factor receptor signaling pathway
GO:8286; insulin receptor signaling pathway
GO:51091; positive regulation of DNA-binding transcription factor activity
GO:30307; positive regulation of cell growth
GO:43154; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:1934; positive regulation of protein phosphorylation
GO:6469; negative regulation of protein kinase activity
GO:51000; positive regulation of nitric-oxide synthase activity
GO:2001240; negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:18107; peptidyl-threonine phosphorylation
GO:2042; cell migration involved in sprouting angiogenesis
GO:60644; mammary gland epithelial cell differentiation
GO:7249; I-kappaB kinase/NF-kappaB signaling
GO:34614; cellular response to reactive oxygen species
GO:38061; NIK/NF-kappaB signaling
GO:45893; positive regulation of transcription, DNA-templated
GO:71276; cellular response to cadmium ion
GO:32270; positive regulation of cellular protein metabolic process
GO:32869; cellular response to insulin stimulus
GO:1903078; positive regulation of protein localization to plasma membrane
GO:8283; cell population proliferation
GO:1901215; negative regulation of neuron death
GO:45429; positive regulation of nitric oxide biosynthetic process
GO:1938; positive regulation of endothelial cell proliferation
GO:90201; negative regulation of release of cytochrome c from mitochondria
GO:6979; response to oxidative stress
GO:46889; positive regulation of lipid biosynthetic process
GO:19221; cytokine-mediated signaling pathway
GO:45600; positive regulation of fat cell differentiation
GO:1902176; negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:31397; negative regulation of protein ubiquitination
GO:32091; negative regulation of protein binding
GO:6809; nitric oxide biosynthetic process
GO:45737; positive regulation of cyclin-dependent protein serine/threonine kinase activity
GO:70141; response to UV-A
GO:1900087; positive regulation of G1/S transition of mitotic cell cycle
GO:45861; negative regulation of proteolysis
GO:1903038; negative regulation of leukocyte cell-cell adhesion
GO:70848; response to growth factor
GO:35655; interleukin-18-mediated signaling pathway
GO:48661; positive regulation of smooth muscle cell proliferation
GO:45725; positive regulation of glycogen biosynthetic process
GO:46326; positive regulation of glucose import
GO:10951; negative regulation of endopeptidase activity
GO:1990090; cellular response to nerve growth factor stimulus
GO:48009; insulin-like growth factor receptor signaling pathway
GO:31295; T cell costimulation
GO:71901; negative regulation of protein serine/threonine kinase activity
GO:1900182; positive regulation of protein localization to nucleus
GO:10748; negative regulation of long-chain fatty acid import across plasma membrane
GO:43536; positive regulation of blood vessel endothelial cell migration
GO:60079; excitatory postsynaptic potential
GO:43488; regulation of mRNA stability
GO:72655; establishment of protein localization to mitochondrion
GO:72656; maintenance of protein location in mitochondrion
GO:32079; positive regulation of endodeoxyribonuclease activity
GO:10975; regulation of neuron projection development
GO:34405; response to fluid shear stress
GO:6924; activation-induced cell death of T cells
GO:3376; sphingosine-1-phosphate receptor signaling pathway
GO:5979; regulation of glycogen biosynthetic process
GO:9408; response to heat
GO:10507; negative regulation of autophagy
GO:10761; fibroblast migration
GO:10907; positive regulation of glucose metabolic process
GO:10918; positive regulation of mitochondrial membrane potential
GO:16242; negative regulation of macroautophagy
GO:31929; TOR signaling
GO:31999; negative regulation of fatty acid beta-oxidation
GO:43276; anoikis
GO:100002; negative regulation of protein kinase activity by protein phosphorylation
GO:140052; cellular response to oxidised low-density lipoprotein particle stimulus
GO:1903721; positive regulation of I-kappaB phosphorylation
GO:2000074; regulation of type B pancreatic cell development
GO:2000402; negative regulation of lymphocyte migration
GO:1649; osteoblast differentiation
GO:1893; maternal placenta development
GO:6954; inflammatory response
GO:7281; germ cell development
GO:8637; apoptotic mitochondrial changes
GO:9725; response to hormone
GO:10033; response to organic substance
GO:10467; gene expression
GO:10629; negative regulation of gene expression
GO:10763; positive regulation of fibroblast migration
GO:10765; positive regulation of sodium ion transport
GO:16567; protein ubiquitination
GO:30163; protein catabolic process
GO:31641; regulation of myelination
GO:31663; lipopolysaccharide-mediated signaling pathway
GO:32094; response to food
GO:32287; peripheral nervous system myelin maintenance
GO:32436; positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:32880; regulation of protein localization
GO:35924; cellular response to vascular endothelial growth factor stimulus
GO:36294; cellular response to decreased oxygen levels
GO:42593; glucose homeostasis
GO:45944; positive regulation of transcription by RNA polymerase II
GO:46622; positive regulation of organ growth
GO:48266; behavioral response to pain
GO:51146; striated muscle cell differentiation
GO:60709; glycogen cell differentiation involved in embryonic placenta development
GO:60716; labyrinthine layer blood vessel development
GO:71363; cellular response to growth factor stimulus
GO:71364; cellular response to epidermal growth factor stimulus
GO:71380; cellular response to prostaglandin E stimulus
GO:97011; cellular response to granulocyte macrophage colony-stimulating factor stimulus
GO:97194; execution phase of apoptosis
GO:1901653; cellular response to peptide
GO:2000010; positive regulation of protein localization to cell surface
GO:2001243; negative regulation of intrinsic apoptotic signaling pathway

Cellular component:

GO:5634; nucleus
GO:5737; cytoplasm
GO:16020; membrane
GO:32991; protein-containing complex
GO:5654; nucleoplasm
GO:5886; plasma membrane
GO:5829; cytosol
GO:15630; microtubule cytoskeleton
GO:31982; vesicle
GO:98794; postsynapse
GO:30027; lamellipodium
GO:31234; extrinsic component of cytoplasmic side of plasma membrane
GO:5739; mitochondrion
GO:5819; spindle
GO:5911; cell-cell junction
GO:36064; ciliary basal body

Function:

GO:5515; protein binding
GO:166; nucleotide binding
GO:4672; protein kinase activity
GO:4674; protein serine/threonine kinase activity
GO:4712; protein serine/threonine/tyrosine kinase activity
GO:5524; ATP binding
GO:16301; kinase activity
GO:16740; transferase activity
GO:106310; protein serine kinase activity
GO:42803; protein homodimerization activity
GO:42802; identical protein binding
GO:5516; calmodulin binding
GO:5547; phosphatidylinositol-3,4,5-trisphosphate binding
GO:43325; phosphatidylinositol-3,4-bisphosphate binding
GO:19899; enzyme binding
GO:71889; 14-3-3 protein binding
GO:30235; nitric-oxide synthase regulator activity
GO:99104; potassium channel activator activity
GO:19901; protein kinase binding

Hide GO terms

Mus musculus

Akt1

Rattus norvegicus

Akt1

GenAge model organism genes