RAC-alpha serine/threonine-protein kinase

NameRAC-alpha serine/threonine-protein kinase
Synonyms2.7.11.1 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 serine/threonine/tyrosine kinase activity
enzyme binding
nitric-oxide synthase regulator activity
ATP binding
phosphatidylinositol-3,4-bisphosphate binding
kinase activity
identical protein binding
14-3-3 protein binding
protein kinase activity
protein serine/threonine kinase activity
phosphatidylinositol-3,4,5-trisphosphate binding
Processes
    response to food
cellular response to prostaglandin E stimulus
osteoblast differentiation
germ cell development
regulation of cell migration
positive regulation of protein localization to nucleus
striated muscle cell differentiation
membrane organization
cellular response to vascular endothelial growth factor stimulus
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of vasoconstriction
blood coagulation
protein catabolic process
negative regulation of cell size
apoptotic process
peptidyl-threonine phosphorylation
negative regulation of autophagy
response to growth hormone
labyrinthine layer blood vessel development
endocrine pancreas development
cellular response to nerve growth factor stimulus
cell differentiation
lipopolysaccharide-mediated signaling pathway
maternal placenta development
regulation of glycogen biosynthetic process
fibroblast growth factor receptor signaling pathway
cellular response to granulocyte macrophage colony-stimulating factor stimulus
execution phase of apoptosis
G-protein coupled receptor signaling pathway
response to heat
positive regulation of lipid biosynthetic process
cellular protein modification process
positive regulation of nitric-oxide synthase activity
programmed cell death
protein import into nucleus, translocation
positive regulation of endodeoxyribonuclease activity
insulin receptor signaling pathway
negative regulation of gene expression
cell proliferation
negative regulation of JNK cascade
response to insulin-like growth factor stimulus
negative regulation of proteolysis
negative regulation of fatty acid beta-oxidation
epidermal growth factor receptor signaling pathway
positive regulation of sodium ion transport
regulation of mRNA stability
positive regulation of establishment of protein localization to plasma membrane
negative regulation of apoptotic process
T cell costimulation
negative regulation of protein kinase activity
hyaluronan metabolic process
activation-induced cell death of T cells
positive regulation of cell growth
insulin-like growth factor receptor signaling pathway
negative regulation of release of cytochrome c from mitochondria
innate immune response
phosphatidylinositol-mediated signaling
response to oxidative stress
glucose transport
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
establishment of protein localization to mitochondrion
aging
gene expression
intracellular signal transduction
signal transduction
apoptotic mitochondrial changes
negative regulation of plasma membrane long-chain fatty acid transport
positive regulation of protein phosphorylation
protein autophosphorylation
inflammatory response
positive regulation of nitric oxide biosynthetic process
positive regulation of fibroblast migration
neurotrophin TRK receptor signaling pathway
maintenance of protein location in mitochondrion
positive regulation of endothelial cell proliferation
small molecule metabolic process
positive regulation of cellular protein metabolic process
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
glycogen biosynthetic process
Fc-epsilon receptor signaling pathway
response to fluid shear stress
translation
positive regulation of blood vessel endothelial cell migration
positive regulation of peptidyl-serine phosphorylation
cell projection organization
intrinsic apoptotic signaling pathway
positive regulation of glucose import
transcription initiation from RNA polymerase II promoter
protein kinase B signaling
nitric oxide biosynthetic process
peripheral nervous system myelin maintenance
regulation of myelination
protein ubiquitination
cellular response to organic cyclic compound
positive regulation of transcription from RNA polymerase II promoter
positive regulation of glucose metabolic process
response to UV-A
peptidyl-serine phosphorylation
cellular response to insulin stimulus
nitric oxide metabolic process
positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
cellular response to epidermal growth factor stimulus
negative regulation of endopeptidase activity
phosphorylation
regulation of translation
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
protein phosphorylation
positive regulation of glycogen biosynthetic process
glucose homeostasis
glycogen cell differentiation involved in embryonic placenta development
mammary gland epithelial cell differentiation
positive regulation of fat cell differentiation
regulation of nitric-oxide synthase activity
cellular response to mechanical stimulus
cellular response to hypoxia
platelet activation
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
regulation of neuron projection development
vascular endothelial growth factor receptor signaling pathway
negative regulation of neuron death
glucose metabolic process
regulation of cell cycle checkpoint
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
Components
    microtubule cytoskeleton
nucleoplasm
vesicle
nucleus
cell-cell junction
cytoplasm
mitochondrion
plasma membrane
protein complex
spindle
ciliary basal body
cytosol
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.
Transmembrane Regions
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 IDNone
GenAtlas IDAKT1
HGNC IDHGNC:391
Chromosome Location14
Locus14q32.32|14q32.32
References
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