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Showing Protein RAC-alpha serine/threonine-protein kinase (HMDBP13421)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 2 metabolites
Identification
HMDB Protein ID HMDBP13421
Secondary Accession Numbers None
Name RAC-alpha serine/threonine-protein kinase
Synonyms
  1. Protein kinase B
  2. Protein kinase B alpha
  3. RAC-PK-alpha
  4. PKB
  5. PKB alpha
Gene Name AKT1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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 (PubMed:11882383, PubMed:21620960, PubMed:21432781). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:21620960, PubMed:21432781). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:21620960, PubMed:21432781). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (PubMed:9632753, PubMed:10400692). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (By similarity). 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 (By similarity). 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 (By similarity). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (PubMed:12107176). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (PubMed:15546921). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). 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 (By similarity). 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) (By similarity). AKT mediates the antiapoptotic effects of IGF-I (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (By similarity). May be involved in the regulation of the placental development (By similarity). 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. Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility. Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation. Phosphorylates 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 (By similarity). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (By similarity). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (By similarity).
Pathways
  • Acute myeloid leukemia
  • Adipocytokine signaling pathway
  • Adrenergic signaling in cardiomyocytes
  • AGE-RAGE signaling pathway in diabetic complications
  • Alzheimer disease
  • AMPK signaling pathway
  • Apelin signaling pathway
  • Apoptosis
  • Autophagy - animal
  • B cell receptor signaling pathway
  • Breast cancer
  • C-type lectin receptor signaling pathway
  • cAMP signaling pathway
  • Carbohydrate digestion and absorption
  • Cellular senescence
  • Central carbon metabolism in cancer
  • cGMP-PKG signaling pathway
  • Chagas disease
  • Chemical carcinogenesis - reactive oxygen species
  • Chemical carcinogenesis - receptor activation
  • Chemokine signaling pathway
  • Choline metabolism in cancer
  • Cholinergic synapse
  • Chronic myeloid leukemia
  • Colorectal cancer
  • Diabetic cardiomyopathy
  • Dopaminergic synapse
  • EGFR tyrosine kinase inhibitor resistance
  • Endocrine resistance
  • Endometrial cancer
  • Epstein-Barr virus infection
  • ErbB signaling pathway
  • Estrogen signaling pathway
  • Fc epsilon RI signaling pathway
  • Fc gamma R-mediated phagocytosis
  • Fluid shear stress and atherosclerosis
  • Focal adhesion
  • FoxO signaling pathway
  • Gastric cancer
  • Glioma
  • Glucagon signaling pathway
  • GnRH secretion
  • Growth hormone synthesis, secretion and action
  • Hepatitis B
  • Hepatitis C
  • Hepatocellular carcinoma
  • Herpes simplex virus 1 infection
  • HIF-1 signaling pathway
  • Human cytomegalovirus infection
  • Human immunodeficiency virus 1 infection
  • Human papillomavirus infection
  • Human T-cell leukemia virus 1 infection
  • Influenza A
  • Insulin resistance
  • Insulin signaling pathway
  • JAK-STAT signaling pathway
  • Kaposi sarcoma-associated herpesvirus infection
  • Lipid and atherosclerosis
  • Longevity regulating pathway
  • Longevity regulating pathway - multiple species
  • MAPK signaling pathway
  • Measles
  • Melanoma
  • mTOR signaling pathway
  • Neurotrophin signaling pathway
  • Neutrophil extracellular trap formation
  • Non-alcoholic fatty liver disease
  • Non-small cell lung cancer
  • Osteoclast differentiation
  • Pancreatic cancer
  • PD-L1 expression and PD-1 checkpoint pathway in cancer
  • Phospholipase D signaling pathway
  • PI3K-Akt signaling pathway
  • Platelet activation
  • Platinum drug resistance
  • Progesterone-mediated oocyte maturation
  • Prolactin signaling pathway
  • Prostate cancer
  • Proteoglycans in cancer
  • Rap1 signaling pathway
  • Ras signaling pathway
  • Regulation of lipolysis in adipocytes
  • Relaxin signaling pathway
  • Renal cell carcinoma
  • Salmonella infection
  • Signaling pathways regulating pluripotency of stem cells
  • Small cell lung cancer
  • Sphingolipid signaling pathway
  • Spinocerebellar ataxia
  • T cell receptor signaling pathway
  • Thyroid hormone signaling pathway
  • TNF signaling pathway
  • Toll-like receptor signaling pathway
  • Toxoplasmosis
  • Tuberculosis
  • VEGF signaling pathway
  • Yersinia infection
Reactions Not Available
GO Classification
Biological Process
regulation of neuron projection development
peptidyl-serine phosphorylation
signal transduction
cellular response to prostaglandin E stimulus
gene expression
positive regulation of apoptotic process
positive regulation of vasoconstriction
translation
negative regulation of release of cytochrome c from mitochondria
maternal placenta development
positive regulation of glycogen biosynthetic process
negative regulation of protein ubiquitination
apoptotic process
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
positive regulation of cell proliferation
negative regulation of apoptotic process
response to hormone stimulus
peripheral nervous system myelin maintenance
cell migration involved in sprouting angiogenesis
positive regulation of glucose metabolic process
negative regulation of cell size
response to oxidative stress
inflammatory response
protein catabolic process
NIK/NF-kappaB signaling
cellular response to tumor necrosis factor
response to growth hormone stimulus
response to DNA damage stimulus
insulin-like growth factor receptor signaling pathway
insulin receptor signaling pathway
positive regulation of endothelial cell migration
positive regulation of protein phosphorylation
response to food
cellular response to vascular endothelial growth factor stimulus
protein kinase B signaling cascade
regulation of translation
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
negative regulation of intrinsic apoptotic signaling pathway
negative regulation of endopeptidase activity
labyrinthine layer blood vessel development
glycogen metabolic process
positive regulation of G1/S transition of mitotic cell cycle
response to organic substance
I-kappaB kinase/NF-kappaB cascade
positive regulation of protein localization to plasma membrane
positive regulation of nitric oxide biosynthetic process
positive regulation of blood vessel endothelial cell migration
cellular response to nerve growth factor stimulus
cellular response to insulin stimulus
positive regulation of glucose import
osteoblast differentiation
cellular response to organic cyclic compound
glucose metabolic process
regulation of protein localization
spinal cord development
positive regulation of cellular protein metabolic process
apoptotic mitochondrial changes
positive regulation of sequence-specific DNA binding transcription factor activity
regulation of cell migration
glucose homeostasis
positive regulation of transcription, DNA-dependent
positive regulation of nitric-oxide synthase activity
germ cell development
cellular response to epidermal growth factor stimulus
positive regulation of transcription from RNA polymerase II promoter
establishment of protein localization to mitochondrion
maintenance of protein location in mitochondrion
activation-induced cell death of T cells
cellular response to decreased oxygen levels
cellular response to peptide
positive regulation of cell growth
cellular response to cadmium ion
execution phase of apoptosis
glycogen cell differentiation involved in embryonic placenta development
hyaluronan metabolic process
cellular response to reactive oxygen species
negative regulation of calcium import into the mitochondrion
regulation of apoptotic process
negative regulation of fatty acid beta-oxidation
negative regulation of leukocyte cell-cell adhesion
negative regulation of long-chain fatty acid import across plasma membrane
negative regulation of lymphocyte migration
negative regulation of proteolysis
protein phosphorylation
phosphatidylinositol 3-kinase signaling
positive regulation of cyclin-dependent protein serine/threonine kinase activity
positive regulation of endodeoxyribonuclease activity
positive regulation of fibroblast migration
positive regulation of I-kappaB phosphorylation
positive regulation of lipid biosynthetic process
positive regulation of mitochondrial membrane potential
positive regulation of organ growth
positive regulation of protein localization to nucleus
regulation of aerobic respiration
cellular response to granulocyte macrophage colony-stimulating factor stimulus
regulation of myelination
response to insulin-like growth factor stimulus
negative regulation of JNK cascade
response to ischemia
response to UV-A
sphingosine-1-phosphate receptor signaling pathway
striated muscle cell differentiation
aging
cell projection organization
negative regulation of protein binding
carbohydrate transport
positive regulation of fat cell differentiation
cellular response to mechanical stimulus
regulation of glycogen biosynthetic process
cellular response to oxidised low-density lipoprotein particle stimulus
lipopolysaccharide-mediated signaling pathway
peptidyl-threonine phosphorylation
cellular response to growth factor stimulus
positive regulation of gene expression
response to fluid shear stress
cellular response to hypoxia
positive regulation of endothelial cell proliferation
protein import into nucleus
positive regulation of smooth muscle cell proliferation
negative regulation of gene expression
positive regulation of peptidyl-serine phosphorylation
negative regulation of superoxide anion generation
glycogen biosynthetic process
phosphorylation
epidermal growth factor receptor signaling pathway
interleukin-18-mediated signaling pathway
intracellular signal transduction
negative regulation of protein kinase activity
negative regulation of autophagy
positive regulation of protein localization to cell surface
positive regulation of sodium ion transport
protein ubiquitination
Cellular Component
cytosol
spindle
protein-containing complex
cytoplasm
mitochondrion
plasma membrane
nucleus
cell-cell junction
nucleoplasm
vesicle
ciliary basal body
Molecular Function
protein kinase binding
kinase activity
phosphatidylinositol-3,4,5-trisphosphate binding
ATP binding
protein homodimerization activity
14-3-3 protein binding
GTPase activating protein binding
nitric-oxide synthase regulator activity
phosphatidylinositol-3,4-bisphosphate binding
potassium channel activator activity
protein serine/threonine/tyrosine kinase activity
protein kinase C binding
protein serine kinase activity
protein kinase activity
protein serine/threonine kinase activity
protein threonine kinase activity
enzyme binding
identical protein binding
calmodulin binding
protein phosphatase 2A binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 480
Molecular Weight 55735.015
Theoretical pI 5.892
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P47196
UniProtKB/Swiss-Prot Entry Name AKT1_RAT
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871. [PubMed:22673903 ]
  2. Nicholson KM, Anderson NG: The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 2002 May;14(5):381-95. doi: 10.1016/s0898-6568(01)00271-6. [PubMed:11882383 ]
  3. Hers I, Vincent EE, Tavare JM: Akt signalling in health and disease. Cell Signal. 2011 Oct;23(10):1515-27. doi: 10.1016/j.cellsig.2011.05.004. Epub 2011 May 17. [PubMed:21620960 ]
  4. Heron-Milhavet L, Khouya N, Fernandez A, Lamb NJ: Akt1 and Akt2: differentiating the aktion. Histol Histopathol. 2011 May;26(5):651-62. doi: 10.14670/HH-26.651. [PubMed:21432781 ]
  5. Konishi H, Shinomura T, Kuroda S, Ono Y, Kikkawa U: Molecular cloning of rat RAC protein kinase alpha and beta and their association with protein kinase C zeta. Biochem Biophys Res Commun. 1994 Nov 30;205(1):817-25. doi: 10.1006/bbrc.1994.2738. [PubMed:7999118 ]
  6. Kitamura T, Ogawa W, Sakaue H, Hino Y, Kuroda S, Takata M, Matsumoto M, Maeda T, Konishi H, Kikkawa U, Kasuga M: Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport. Mol Cell Biol. 1998 Jul;18(7):3708-17. doi: 10.1128/MCB.18.7.3708. [PubMed:9632753 ]
  7. Takata M, Ogawa W, Kitamura T, Hino Y, Kuroda S, Kotani K, Klip A, Gingras AC, Sonenberg N, Kasuga M: Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1). J Biol Chem. 1999 Jul 16;274(29):20611-8. doi: 10.1074/jbc.274.29.20611. [PubMed:10400692 ]
  8. Berwick DC, Hers I, Heesom KJ, Moule SK, Tavare JM: The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes. J Biol Chem. 2002 Sep 13;277(37):33895-900. doi: 10.1074/jbc.M204681200. Epub 2002 Jul 9. [PubMed:12107176 ]
  9. Berwick DC, Dell GC, Welsh GI, Heesom KJ, Hers I, Fletcher LM, Cooke FT, Tavare JM: Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles. J Cell Sci. 2004 Dec 1;117(Pt 25):5985-93. doi: 10.1242/jcs.01517. Epub 2004 Nov 16. [PubMed:15546921 ]
  10. Liu Z, Ahn JY, Liu X, Ye K: Ebp1 isoforms distinctively regulate cell survival and differentiation. Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10917-22. doi: 10.1073/pnas.0602923103. Epub 2006 Jul 10. [PubMed:16832058 ]