UniProt Accession

 AKT1_MOUSE; P31750; Q62274; Q6GSA6 

Genbank Protein ID

 X65687; AF534134; M94335; AK154936; CH466549; BC066018 

Genbank Nucleotide ID

 CAA46620.1; AAN04036.1; AAA18254.1; BAE32937.1; EDL18586.1; AAH66018.1 

Protein Name

 RAC-alpha serine/threonine-protein kinase 

Protein Synonyms/Alias

 AKT1 kinase; Protein kinase B; PKB; Protein kinase B alpha; PKB alpha; Proto-oncogene c-Akt; RAC-PK-alpha; Thymoma viral proto-oncogene 

Gene Name

 Akt1 

Gene Synonyms/Alias

 Akt; Rac 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
30	RPRYFLLKNDGTFIG	ubiquitination	[1]
276	NVVYRDLKLENLMLD	acetylation	[2]
276	NVVYRDLKLENLMLD	ubiquitination	[1]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 

Functional Description

 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. 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 (By similarity). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (By similarity). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (By similarity). 

Sequence Annotation

 DOMAIN 5 108 PH.
 DOMAIN 150 408 Protein kinase.
 DOMAIN 409 480 AGC-kinase C-terminal.
 NP_BIND 156 164 ATP (By similarity).
 REGION 14 19 Inositol-(1,3,4,5)-tetrakisphosphate
 REGION 23 25 Inositol-(1,3,4,5)-tetrakisphosphate
 REGION 228 230 Inhibitor binding (By similarity).
 ACT_SITE 274 274 Proton acceptor (By similarity).
 BINDING 53 53 Inositol-(1,3,4,5)-tetrakisphosphate (By
 BINDING 86 86 Inositol-(1,3,4,5)-tetrakisphosphate (By
 BINDING 161 161 Inhibitor; via amide nitrogen (By
 BINDING 179 179 ATP.
 BINDING 230 230 Inhibitor; via amide nitrogen (By
 BINDING 234 234 Inhibitor (By similarity).
 BINDING 292 292 Inhibitor (By similarity).
 MOD_RES 14 14 N6-acetyllysine (By similarity).
 MOD_RES 20 20 N6-acetyllysine (By similarity).
 MOD_RES 124 124 Phosphoserine.
 MOD_RES 126 126 Phosphoserine; alternate.
 MOD_RES 129 129 Phosphoserine; alternate.
 MOD_RES 176 176 Phosphotyrosine; by TNK2.
 MOD_RES 308 308 Phosphothreonine; by PDPK1.
 MOD_RES 450 450 Phosphothreonine; by MTOR.
 MOD_RES 473 473 Phosphoserine; by MTOR; alternate
 MOD_RES 474 474 Phosphotyrosine (By similarity).
 CARBOHYD 126 126 O-linked (GlcNAc...); alternate (By
 CARBOHYD 129 129 O-linked (GlcNAc...); alternate (By
 CARBOHYD 305 305 O-linked (GlcNAc...) (By similarity).
 CARBOHYD 312 312 O-linked (GlcNAc...) (By similarity).
 CARBOHYD 473 473 O-linked (GlcNAc...); alternate.
 DISULFID 60 77 By similarity.
 DISULFID 296 310 By similarity.  

Keyword

 Acetylation; Apoptosis; ATP-binding; Carbohydrate metabolism; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Disulfide bond; Glucose metabolism; Glycogen biosynthesis; Glycogen metabolism; Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Sugar transport; Transferase; Translation regulation; Transport; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 480 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0005819; C:spindle; IDA:MGI.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0030235; F:nitric-oxide synthase regulator activity; IEA:Compara.
 GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IEA:Compara.
 GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IEA:Compara.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0006924; P:activation-induced cell death of T cells; ISO:MGI.
 GO:0007568; P:aging; IEA:Compara.
 GO:0042640; P:anagen; IMP:MGI.
 GO:0008637; P:apoptotic mitochondrial changes; IDA:MGI.
 GO:0030030; P:cell projection organization; ISO:MGI.
 GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB.
 GO:0071456; P:cellular response to hypoxia; IEA:Compara.
 GO:0007010; P:cytoskeleton organization; TAS:UniProtKB.
 GO:0031018; P:endocrine pancreas development; TAS:Reactome.
 GO:0097194; P:execution phase of apoptosis; IDA:MGI.
 GO:0007281; P:germ cell development; IDA:MGI.
 GO:0042593; P:glucose homeostasis; IMP:MGI.
 GO:0006006; P:glucose metabolic process; IMP:MGI.
 GO:0015758; P:glucose transport; IMP:UniProtKB.
 GO:0005978; P:glycogen biosynthetic process; IEA:UniProtKB-KW.
 GO:0060709; P:glycogen cell differentiation involved in embryonic placenta development; IMP:MGI.
 GO:0005977; P:glycogen metabolic process; IMP:MGI.
 GO:0006954; P:inflammatory response; IDA:MGI.
 GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
 GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
 GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
 GO:0001893; P:maternal placenta development; IMP:MGI.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0045792; P:negative regulation of cell size; ISO:MGI.
 GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
 GO:0031999; P:negative regulation of fatty acid beta-oxidation; IEA:Compara.
 GO:0046329; P:negative regulation of JNK cascade; IEA:Compara.
 GO:0010748; P:negative regulation of plasma membrane long-chain fatty acid transport; IEA:Compara.
 GO:0006469; P:negative regulation of protein kinase activity; IEA:Compara.
 GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:UniProtKB.
 GO:0001649; P:osteoblast differentiation; IGI:MGI.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
 GO:0032287; P:peripheral nervous system myelin maintenance; IMP:MGI.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IEA:Compara.
 GO:0030307; P:positive regulation of cell growth; IEA:Compara.
 GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IEA:Compara.
 GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IEA:Compara.
 GO:0045600; P:positive regulation of fat cell differentiation; IEA:Compara.
 GO:0046326; P:positive regulation of glucose import; IEA:Compara.
 GO:0045725; P:positive regulation of glycogen biosynthetic process; IEA:Compara.
 GO:0046889; P:positive regulation of lipid biosynthetic process; IEA:Compara.
 GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Compara.
 GO:0051000; P:positive regulation of nitric-oxide synthase activity; IEA:Compara.
 GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Compara.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:MGI.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IEA:Compara.
 GO:0010765; P:positive regulation of sodium ion transport; IMP:MGI.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IGI:MGI.
 GO:0045907; P:positive regulation of vasoconstriction; IEA:Compara.
 GO:0030163; P:protein catabolic process; IDA:MGI.
 GO:0000060; P:protein import into nucleus, translocation; IEA:Compara.
 GO:0043491; P:protein kinase B signaling cascade; IGI:MGI.
 GO:0016567; P:protein ubiquitination; IDA:MGI.
 GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
 GO:0010975; P:regulation of neuron projection development; IDA:UniProtKB.
 GO:0032880; P:regulation of protein localization; IDA:MGI.
 GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
 GO:0034405; P:response to fluid shear stress; IEA:Compara.
 GO:0032094; P:response to food; IDA:MGI.
 GO:0070141; P:response to UV-A; IEA:Compara.
 GO:0051146; P:striated muscle cell differentiation; IGI:MGI.
 GO:0006412; P:translation; IEA:Compara. 

Interpro

 IPR000961; AGC-kinase_C.
 IPR011009; Kinase-like_dom.
 IPR011993; PH_like_dom.
 IPR017892; Pkinase_C.
 IPR001849; Pleckstrin_homology.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00169; PH
 PF00069; Pkinase
 PF00433; Pkinase_C 

SMART

 SM00233; PH
 SM00133; S_TK_X
 SM00220; S_TKc 

PROSITE

 PS51285; AGC_KINASE_CTER
 PS50003; PH_DOMAIN
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS