CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006014
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 RAC-alpha serine/threonine-protein kinase 
Protein Synonyms/Alias
 Protein kinase B; PKB; Protein kinase B alpha; PKB alpha; Proto-oncogene c-Akt; RAC-PK-alpha 
Gene Name
 AKT1 
Gene Synonyms/Alias
 PKB; RAC 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
8MSDVAIVKEGWLHKRubiquitination[1, 2]
14VKEGWLHKRGEYIKTubiquitination[2]
30RPRYFLLKNDGTFIGubiquitination[1, 2]
39DGTFIGYKERPQDVDubiquitination[2]
140EMEVSLAKPKHRVTMubiquitination[2]
158EYLKLLGKGTFGKVIubiquitination[2]
268LDYLHSEKNVVYRDLubiquitination[2]
276NVVYRDLKLENLMLDubiquitination[1, 2]
297ITDFGLCKEGIKDGAubiquitination[2]
301GLCKEGIKDGATMKTubiquitination[2]
377RTLGPEAKSLLSGLLubiquitination[2, 3]
400GGGSEDAKEIMQHRFubiquitination[2]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
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. 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. 
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.
 ACT_SITE 274 274 Proton acceptor (By similarity).
 BINDING 53 53 Inositol-(1,3,4,5)-tetrakisphosphate.
 BINDING 86 86 Inositol-(1,3,4,5)-tetrakisphosphate.
 BINDING 161 161 Inhibitor; via amide nitrogen.
 BINDING 179 179 ATP (By similarity).
 BINDING 230 230 Inhibitor; via amide nitrogen.
 BINDING 234 234 Inhibitor.
 BINDING 292 292 Inhibitor.
 MOD_RES 14 14 N6-acetyllysine.
 MOD_RES 20 20 N6-acetyllysine.
 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 (By
 MOD_RES 473 473 Phosphoserine; by MTOR; alternate.
 MOD_RES 474 474 Phosphotyrosine.
 CARBOHYD 126 126 O-linked (GlcNAc...); alternate.
 CARBOHYD 129 129 O-linked (GlcNAc...); alternate.
 CARBOHYD 305 305 O-linked (GlcNAc...).
 CARBOHYD 312 312 O-linked (GlcNAc...).
 CARBOHYD 473 473 O-linked (GlcNAc...); alternate (By
 DISULFID 60 77
 DISULFID 296 310 By similarity.  
Keyword
 3D-structure; Acetylation; Apoptosis; ATP-binding; Carbohydrate metabolism; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Disease mutation; Disulfide bond; Glucose metabolism; Glycogen biosynthesis; Glycogen metabolism; Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; 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
MSDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQREA PLNNFSVAQC 60
QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT TAIQTVADGL KKQEEEEMDF 120
RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI 180
LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS 240
RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI 300
KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL 360
ILMEEIRFPR TLGPEAKSLL SGLLKKDPKQ RLGGGSEDAK EIMQHRFFAG IVWQHVYEKK 420
LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA 480 
Gene Ontology
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0030027; C:lamellipodium; IEA:Compara.
 GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0005819; C:spindle; IEA:Compara.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0019899; F:enzyme binding; ISS:BHF-UCL.
 GO:0030235; F:nitric-oxide synthase regulator activity; IMP:BHF-UCL.
 GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
 GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0006924; P:activation-induced cell death of T cells; IMP:MGI.
 GO:0007568; P:aging; IEA:Compara.
 GO:0042640; P:anagen; IEA:Compara.
 GO:0008637; P:apoptotic mitochondrial changes; IEA:Compara.
 GO:0030030; P:cell projection organization; IEA:Compara.
 GO:0008283; P:cell proliferation; TAS:UniProtKB.
 GO:0016044; P:cellular membrane organization; TAS:Reactome.
 GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Compara.
 GO:0071456; P:cellular response to hypoxia; IEA:Compara.
 GO:0031018; P:endocrine pancreas development; TAS:Reactome.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:ProtInc.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0007281; P:germ cell development; IEA:Compara.
 GO:0042593; P:glucose homeostasis; IEA:Compara.
 GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
 GO:0015758; P:glucose transport; IEA:Compara.
 GO:0005978; P:glycogen biosynthetic process; IEA:UniProtKB-KW.
 GO:0060709; P:glycogen cell differentiation involved in embryonic placenta development; IEA:Compara.
 GO:0006954; P:inflammatory response; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
 GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:UniProtKB.
 GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
 GO:0060716; P:labyrinthine layer blood vessel development; IEA:Compara.
 GO:0060644; P:mammary gland epithelial cell differentiation; TAS:UniProtKB.
 GO:0001893; P:maternal placenta development; IEA:Compara.
 GO:0016071; P:mRNA metabolic process; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0010507; P:negative regulation of autophagy; IMP:BHF-UCL.
 GO:0045792; P:negative regulation of cell size; IEA:Compara.
 GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
 GO:0031999; P:negative regulation of fatty acid beta-oxidation; IMP:BHF-UCL.
 GO:0046329; P:negative regulation of JNK cascade; IEA:Compara.
 GO:0010748; P:negative regulation of plasma membrane long-chain fatty acid transport; IMP:BHF-UCL.
 GO:0006469; P:negative regulation of protein kinase activity; IMP:BHF-UCL.
 GO:0045861; P:negative regulation of proteolysis; IMP:BHF-UCL.
 GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0006809; P:nitric oxide biosynthetic process; TAS:ProtInc.
 GO:0001649; P:osteoblast differentiation; IEA:Compara.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
 GO:0032287; P:peripheral nervous system myelin maintenance; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:DFLAT.
 GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
 GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
 GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IMP:BHF-UCL.
 GO:0045600; P:positive regulation of fat cell differentiation; IMP:BHF-UCL.
 GO:0046326; P:positive regulation of glucose import; IMP:BHF-UCL.
 GO:0045725; P:positive regulation of glycogen biosynthetic process; IMP:BHF-UCL.
 GO:0046889; P:positive regulation of lipid biosynthetic process; IMP:BHF-UCL.
 GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL.
 GO:0051000; P:positive regulation of nitric-oxide synthase activity; IMP:BHF-UCL.
 GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Compara.
 GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:0010765; P:positive regulation of sodium ion transport; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0045907; P:positive regulation of vasoconstriction; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; TAS:UniProtKB.
 GO:0030163; P:protein catabolic process; IEA:Compara.
 GO:0000060; P:protein import into nucleus, translocation; IMP:UniProtKB.
 GO:0043491; P:protein kinase B signaling cascade; IEA:Compara.
 GO:0016567; P:protein ubiquitination; IEA:Compara.
 GO:1901976; P:regulation of cell cycle checkpoint; TAS:UniProtKB.
 GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
 GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
 GO:0034405; P:response to fluid shear stress; IMP:BHF-UCL.
 GO:0032094; P:response to food; IEA:Compara.
 GO:0009408; P:response to heat; TAS:ProtInc.
 GO:0070141; P:response to UV-A; IDA:BHF-UCL.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome.
 GO:0051146; P:striated muscle cell differentiation; IEA:Compara.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 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