Akt1
entrez
24185
canonical
uniprot
P47196
canonical
ensembl
ENSRNOG00000028629
resolver
ensembl
ENSRNOG00055028853
resolver
ensembl
ENSRNOG00060026743
resolver
ensembl
ENSRNOG00065028102
resolver
ensp
ENSRNOP00000090205
resolver
ensp
ENSRNOP00055041243
resolver
ensp
ENSRNOP00060038823
resolver
ensp
ENSRNOP00065039837
resolver
enst
ENSRNOT00000114705
resolver
enst
ENSRNOT00055050101
resolver
enst
ENSRNOT00060046687
resolver
enst
ENSRNOT00065048586
resolver
genesymbol
Akt1
resolver
uniprot_entry
AKT1_RAT
resolver
activity_regulation
ACTIVITY REGULATION: Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation.
uniprot
proteins
amino_acid_sequence
MNDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVEQRESPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKRQEEETMDFRSGSPSDNSGAEEMEVALAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPTQRLGGGSEDAKEIMQHRFFANIVWQDVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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:9228007, PubMed:11882383, PubMed:21432781, PubMed:21620960). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:21432781, PubMed:21620960). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:21432781, PubMed:21620960). 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:10400692, PubMed:9632753). 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 also regulates 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 also regulates 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 the mTORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. Also regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CASTOR1 and DEPDC5. 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). Part of a positive feedback loop of mTORC2 signaling by mediating phosphorylation of MAPKAP1/SIN1, promoting mTORC2 activation (By similarity). 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). 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 1 (IGF1) (By similarity). AKT mediates the antiapoptotic effects of IGF1 (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). Acts as a negative regulator of the cGAS-STING pathway by mediating phosphorylation of CGAS during mitosis, leading to its inhibition (By similarity). Acts as a regulator of mitochondrial calcium uptake by mediating phosphorylation of MICU1 in the mitochondrial intermembrane space, impairing MICU1 maturation (By similarity). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (By similarity). In response to LPAR1 receptor pathway activation, phosphorylates Rabin8/RAB3IP which alters its activity and phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling (By similarity). {ECO:0000250|UniProtKB:P31749, ECO:0000250|UniProtKB:P31750, ECO:0000269|PubMed:10400692, ECO:0000269|PubMed:12107176, ECO:0000269|PubMed:15546921, ECO:0000269|PubMed:9228007, ECO:0000269|PubMed:9632753, ECO:0000303|PubMed:11882383, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}.
uniprot
proteins
mass_dalton
55735
uniprot
proteins
mutagenesis
MUTAGEN 179; /note="K->A,D: Lacks kinase activity. Inhibits insulin-induced activation of glycogen synthase when expressed."; /evidence="ECO:0000269|PubMed:10400692, ECO:0000269|PubMed:9228007, ECO:0000269|PubMed:9632753"; MUTAGEN 308; /note="T->A: Inhibits insulin-induced activation of endogenous Akt1, insulin-stimulated protein synthesis, insulin-induced activation of glycogen synthase and insulin-induced phosphorylation of 4E-BP1 in a dominant negative manner when overexpressed; when associated with A-473."; /evidence="ECO:0000269|PubMed:10400692, ECO:0000269|PubMed:9632753"; MUTAGEN 473; /note="S->A: Inhibits insulin-induced activation of endogenous Akt1, insulin-stimulated protein synthesis, insulin-induced activation of glycogen synthase and insulin-induced phosphorylation of 4E-BP1 in a dominant negative manner when overexpressed; when associated with A-308."; /evidence="ECO:0000269|PubMed:10400692, ECO:0000269|PubMed:9632753
uniprot
proteins
post_translational_modification
PTM: O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating phosphorylation at Thr-308 via disrupting the interaction between AKT1 and PDPK1. O-GlcNAcylation at Ser-473 also probably interferes with phosphorylation at this site. {ECO:0000250|UniProtKB:P31749}.; PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity (PubMed:10400692, PubMed:9228007). Phosphorylation of the activation loop at Thr-308 by PDPK1/PDK1 is a prerequisite for full activation (By similarity). Phosphorylation by mTORC2 in response to growth factors plays a key role in AKT1 activation: mTORC2 phosphorylates different sites depending on the context, such as Thr-450, Ser-473, Ser-477 or Thr-479, thereby facilitating subsequent phosphorylation of the activation loop by PDPK1/PDK1 (By similarity). Phosphorylation at Ser-473 by mTORC2 promotes ubiquitination and degradation by the proteasome (By similarity). Also phosphorylated at Ser-477 and Thr-479 by CDK2, facilitating subsequent phosphorylation of the activation loop by PDPK1/PDK1 (By similarity). Activated TNK2 phosphorylates it on Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA (By similarity). This phosphorylated form localizes to the cell membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to its activation (By similarity). Phosphorylated at Thr-308 and Ser-473 by IKBKE and TBK1 (By similarity). Ser-473 phosphorylation is enhanced by interaction with AGAP2 isoform 2 (PIKE-A) (By similarity). Ser-473 phosphorylation is enhanced by signaling through activated FLT3 (By similarity). Ser-473 is dephosphorylated by PHLPP (By similarity). Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase (By similarity). The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase (By similarity). Ser-473 is dephosphorylated by CPPED1, leading to termination of signaling (By similarity). AIM2 acts as an inhibitor of AKT1 by inhibiting phosphorylation Ser-473: AIM2 acts both by inhibiting the activity of PRKDC/DNA-PK kinase and promoting dephosphorylation by PP2A phosphatase (By similarity). {ECO:0000250|UniProtKB:P31749, ECO:0000250|UniProtKB:P31750, ECO:0000269|PubMed:10400692, ECO:0000269|PubMed:9228007}.; PTM: Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation. When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome. Also ubiquitinated by TRIM13 leading to its proteasomal degradation. Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P31749, ECO:0000250|UniProtKB:P31750}.; PTM: Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases EP300 and KAT2B. Acetylation results in reduced phosphorylation and inhibition of activity. Deacetylated at Lys-14 and Lys-20 by SIRT1. SIRT1-mediated deacetylation relieves the inhibition (By similarity). {ECO:0000250|UniProtKB:P31749}.; PTM: Cleavage by caspase-3/CASP3 (By similarity). Cleaved at the caspase-3 consensus site Asp-462 during apoptosis, resulting in down-regulation of the AKT signaling pathway and decreased cell survival (By similarity). {ECO:0000250|UniProtKB:P31749, ECO:0000250|UniProtKB:P31750}.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
RAC subfamily
uniprot
proteins
pubmed
10400692
uniprot
proteins
pubmed
11882383
uniprot
proteins
pubmed
12107176
uniprot
proteins
pubmed
15546921
uniprot
proteins
pubmed
16832058
uniprot
proteins
pubmed
21432781
uniprot
proteins
pubmed
21620960
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
7999118
uniprot
proteins
pubmed
9228007
uniprot
proteins
pubmed
9632753
uniprot
proteins
sequence_length
480
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P31750}. Nucleus {ECO:0000250|UniProtKB:P31749}. Cell membrane {ECO:0000269|PubMed:9228007}. Mitochondrion intermembrane space {ECO:0000250|UniProtKB:P31750}. Note=Nucleus after activation by integrin-linked protein kinase 1 (ILK1). 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. Colocalizes with WDFY2 in intracellular vesicles (By similarity). Also localizes to mitochondrial intermembrane space in response to rapamycin treatment (By similarity). {ECO:0000250|UniProtKB:P31749, ECO:0000250|UniProtKB:P31750}.
uniprot
proteins