RAC-alpha serine/threonine-protein kinase

NameRAC-alpha serine/threonine-protein kinase
Synonyms
  • 2.7.11.1
  • PKB
  • PKB alpha
  • Protein kinase B
  • Protein kinase B alpha
  • Proto-oncogene c-Akt
  • RAC
  • RAC-PK-alpha
Gene NameAKT1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000853|RAC-alpha serine/threonine-protein kinase
MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQC
QLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDF
RSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKI
LKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLS
RERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGI
KDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFEL
ILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKK
LSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA
Number of residues480
Molecular Weight55686.035
Theoretical pI5.96
GO Classification
Functions
  • protein kinase activity
  • phosphatidylinositol-3,4,5-trisphosphate binding
  • protein serine/threonine kinase activity
  • protein serine/threonine/tyrosine kinase activity
  • phosphatidylinositol-3,4-bisphosphate binding
  • 14-3-3 protein binding
  • nitric-oxide synthase regulator activity
  • ATP binding
  • kinase activity
  • identical protein binding
  • enzyme binding
Processes
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
  • negative regulation of proteolysis
  • negative regulation of gene expression
  • negative regulation of JNK cascade
  • cellular response to epidermal growth factor stimulus
  • response to insulin-like growth factor stimulus
  • cellular response to insulin stimulus
  • nitric oxide metabolic process
  • cell proliferation
  • negative regulation of protein kinase activity
  • T cell costimulation
  • hyaluronan metabolic process
  • cellular response to mechanical stimulus
  • activation-induced cell death of T cells
  • positive regulation of fat cell differentiation
  • regulation of nitric-oxide synthase activity
  • gene expression
  • aging
  • osteoblast differentiation
  • establishment of protein localization to mitochondrion
  • response to food
  • cellular response to prostaglandin E stimulus
  • protein catabolic process
  • small molecule metabolic process
  • negative regulation of cell size
  • positive regulation of endothelial cell proliferation
  • blood coagulation
  • apoptotic process
  • maintenance of protein location in mitochondrion
  • positive regulation of vasoconstriction
  • maternal placenta development
  • transcription initiation from RNA polymerase II promoter
  • regulation of glycogen biosynthetic process
  • intrinsic apoptotic signaling pathway
  • positive regulation of glucose import
  • fibroblast growth factor receptor signaling pathway
  • cell projection organization
  • lipopolysaccharide-mediated signaling pathway
  • protein import into nucleus, translocation
  • positive regulation of endodeoxyribonuclease activity
  • peptidyl-serine phosphorylation
  • programmed cell death
  • positive regulation of glucose metabolic process
  • insulin receptor signaling pathway
  • response to UV-A
  • positive regulation of nitric-oxide synthase activity
  • regulation of mRNA stability
  • glucose homeostasis
  • positive regulation of establishment of protein localization to plasma membrane
  • mammary gland epithelial cell differentiation
  • positive regulation of glycogen biosynthetic process
  • negative regulation of apoptotic process
  • glycogen cell differentiation involved in embryonic placenta development
  • positive regulation of sodium ion transport
  • phosphatidylinositol-mediated signaling
  • glucose transport
  • glucose metabolic process
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
  • response to oxidative stress
  • negative regulation of neuron death
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • regulation of cell cycle checkpoint
  • protein autophosphorylation
  • positive regulation of nitric oxide biosynthetic process
  • positive regulation of fibroblast migration
  • cellular response to vascular endothelial growth factor stimulus
  • inflammatory response
  • positive regulation of sequence-specific DNA binding transcription factor activity
  • neurotrophin TRK receptor signaling pathway
  • response to fluid shear stress
  • cell differentiation
  • positive regulation of blood vessel endothelial cell migration
  • endocrine pancreas development
  • translation
  • cellular response to nerve growth factor stimulus
  • positive regulation of peptidyl-serine phosphorylation
  • regulation of myelination
  • cellular response to organic cyclic compound
  • cellular protein modification process
  • response to heat
  • protein ubiquitination
  • positive regulation of lipid biosynthetic process
  • positive regulation of transcription from RNA polymerase II promoter
  • negative regulation of endopeptidase activity
  • regulation of translation
  • epidermal growth factor receptor signaling pathway
  • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
  • negative regulation of fatty acid beta-oxidation
  • phosphorylation
  • protein phosphorylation
  • cellular response to hypoxia
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
  • innate immune response
  • regulation of neuron projection development
  • positive regulation of cell growth
  • insulin-like growth factor receptor signaling pathway
  • platelet activation
  • negative regulation of release of cytochrome c from mitochondria
  • vascular endothelial growth factor receptor signaling pathway
  • membrane organization
  • germ cell development
  • signal transduction
  • positive regulation of protein localization to nucleus
  • positive regulation of protein phosphorylation
  • striated muscle cell differentiation
  • intracellular signal transduction
  • apoptotic mitochondrial changes
  • regulation of cell migration
  • negative regulation of plasma membrane long-chain fatty acid transport
  • labyrinthine layer blood vessel development
  • peptidyl-threonine phosphorylation
  • negative regulation of autophagy
  • Fc-epsilon receptor signaling pathway
  • response to growth hormone
  • positive regulation of cellular protein metabolic process
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  • glycogen biosynthetic process
  • G-protein coupled receptor signaling pathway
  • cellular response to granulocyte macrophage colony-stimulating factor stimulus
  • execution phase of apoptosis
  • protein kinase B signaling
  • nitric oxide biosynthetic process
  • peripheral nervous system myelin maintenance
Components
  • microtubule cytoskeleton
  • ciliary basal body
  • nucleus
  • cytosol
  • plasma membrane
  • spindle
  • nucleoplasm
  • cytoplasm
  • mitochondrion
  • protein complex
  • vesicle
  • cell-cell junction
General FunctionProtein serine/threonine/tyrosine kinase activity
Specific FunctionAKT1 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. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53.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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID190828
UniProtKB IDP31749
UniProtKB Entry NameAKT1_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0021923|RAC-alpha serine/threonine-protein kinase (AKT1)
ATGAGCGACGTGGCTATTGTGAAGGAGGGTTGGCTGCACAAACGAGGGGAGTACATCAAG
ACCTGGCGGCCACGCTACTTCCTCCTCAAGAATGATGGCACCTTCATTGGCTACAAGGAG
CGGCCGCAGGATGTGGACCAACGTGAGGCTCCCCTCAACAACTTCTCTGTGGCGCAGTGC
CAGCTGATGAAGACGGAGCGGCCCCGGCCCAACACCTTCATCATCCGCTGCCTGCAGTGG
ACCACTGTCATCGAACGCACCTTCCATGTGGAGACTCCTGAGGAGCGGGAGGAGTGGACA
ACCGCCATCCAGACTGTGGCTGACGGCCTCAAGAAGCAGGAGGAGGAGGAGATGGACTTC
CGGTCGGGCTCACCCAGTGACAACTCAGGGGCTGAAGAGATGGAGGTGTCCCTGGCCAAG
CCCAAGCACCGCGTGACCATGAACGAGTTTGAGTACCTGAAGCTGCTGGGCAAGGGCACT
TTCGGCAAGGTGATCCTGGTGAAGGAGAAGGCCACAGGCCGCTACTACGCCATGAAGATC
CTCAAGAAGGAAGTCATCGTGGCCAAGGACGAGGTGGCCCACACACTCACCGAGAACCGC
GTCCTGCAGAACTCCAGGCACCCCTTCCTCACAGCCCTGAAGTACTCTTTCCAGACCCAC
GACCGCCTCTGCTTTGTCATGGAGTACGCCAACGGGGGCGAGCTGTTCTTCCACCTGTCC
CGGGAGCGTGTGTTCTCCGAGGACCGGGCCCGCTTCTATGGCGCTGAGATTGTGTCAGCC
CTGGACTACCTGCACTCGGAGAAGAACGTGGTGTACCGGGACCTCAAGCTGGAGAACCTC
ATGCTGGACAAGGACGGGCACATTAAGATCACAGACTTCGGGCTGTGCAAGGAGGGGATC
AAGGACGGTGCCACCATGAAGACCTTTTGCGGCACACCTGAGTACCTGGCCCCCGAGGTG
CTGGAGGACAATGACTACGGCCGTGCAGTGGACTGGTGGGGGCTGGGCGTGGTCATGTAC
GAGATGATGTGCGGTCGCCTGCCCTTCTACAACCAGGACCATGAGAAGCTTTTTGAGCTC
ATCCTCATGGAGGAGATCCGCTTCCCGCGCACGCTTGGTCCCGAGGCCAAGTCCTTGCTT
TCAGGGCTGCTCAAGAAGGACCCCAAGCAGAGGCTTGGCGGGGGCTCCGAGGACGCCAAG
GAGATCATGCAGCATCGCTTCTTTGCCGGTATCGTGTGGCAGCACGTGTACGAGAAGAAG
CTCAGCCCACCCTTCAAGCCCCAGGTCACGTCGGAGACTGACACCAGGTATTTTGATGAG
GAGTTCACGGCCCAGATGATCACCATCACACCACCTGACCAAGATGACAGCATGGAGTGT
GTGGACAGCGAGCGCAGGCCCCACTTCCCCCAGTTCTCCTACTCGGCCAGCGGCACGGCC
TGA
GenBank Gene IDM63167
GeneCard IDNot Available
GenAtlas IDAKT1
HGNC IDHGNC:391
Chromosome Location14
Locus14q32.32|14q32.32
References
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