Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  RAC-alpha serine/threonine-protein kinase  

UniProtKB / Swiss-Prot ID :  AKT1_HUMAN

Gene Name (Synonyms) : 
AKT1, PKB, RAC  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Nucleus. Cell membrane. 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  

Protein 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. 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. 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. 

Protein Sequence MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTERPRP...
Predicted Secondary Structure CCCCCEEEECEEEEECCCCCCCCCEEEEEECCCCHHHHHHHHHHHCCCCCCCCEEEECCCCCCCCCCCCC...
Protein Variant
LocationDescription
17E -> K (in PROTEUSS and breast cancer;also detected in colorectal and ovarian
167V -> A (in dbSNP:rs11555433). VAR_051617
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)VAIVKEGWL
CCEEEECEE
44.38Phosphositeplus
Link
14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)GWLHKRGEY
CEEEEECCC
60.99Phosphositeplus
Link
14N6-acetyllysine.GWLHKRGEY
CEEEEECCC
60.99UniProtKB
Link
20N6-acetyllysine.GEYIKTWRP
CCCCCCCCC
40.93UniProtKB
Link
30Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)YFLLKNDGT
EEEEECCCC
55.96Phosphositeplus
Link
72PhosphothreoninePRPNTFIIR
CCCCCCEEE
20.92Phosphositeplus
Link
122PhosphoserineMDFRSGSPS
CCCCCCCCC
43.55HPRD
Link-
122PhosphoserineMDFRSGSPS
CCCCCCCCC
43.55PhosphoELM
Link-
122PhosphoserineMDFRSGSPS
CCCCCCCCC
43.55Phosphositeplus
Link-
124PhosphoserineFRSGSPSDN
CCCCCCCCC
23.60HPRD
Link-
124PhosphoserineFRSGSPSDN
CCCCCCCCC
23.60PhosphoELM
Link-
124PhosphoserineFRSGSPSDN
CCCCCCCCC
23.60Phosphositeplus
Link-
124PhosphoserineFRSGSPSDN
CCCCCCCCC
23.60SysPTM
Link-
124Phosphoserine.FRSGSPSDN
CCCCCCCCC
23.60UniProtKB
Link-
126O-linked (GlcNAc)SGSPSDNSG
CCCCCCCCC
51.63Phosphositeplus
Link-
126O-linked (GlcNAc...).SGSPSDNSG
CCCCCCCCC
51.63UniProtKB
Link-
126PhosphoserineSGSPSDNSG
CCCCCCCCC
51.63HPRD
Link-
126PhosphoserineSGSPSDNSG
CCCCCCCCC
51.63PhosphoELM
Link-
126PhosphoserineSGSPSDNSG
CCCCCCCCC
51.63Phosphositeplus
Link-
126PhosphoserineSGSPSDNSG
CCCCCCCCC
51.63SysPTM
Link-
126Phosphoserine.SGSPSDNSG
CCCCCCCCC
51.63UniProtKB
Link-
129O-linked (GlcNAc)PSDNSGAEE
CCCCCCCCC
44.35Phosphositeplus
Link-
129O-linked (GlcNAc...).PSDNSGAEE
CCCCCCCCC
44.35UniProtKB
Link-
129PhosphoserinePSDNSGAEE
CCCCCCCCC
44.35HPRD
Link-
129PhosphoserinePSDNSGAEE
CCCCCCCCC
44.35Phosphositeplus
Link-
129PhosphoserinePSDNSGAEE
CCCCCCCCC
44.35SysPTM
Link-
129Phosphoserine (CK2_alpha)PSDNSGAEE
CCCCCCCCC
44.35PhosphoELM
Link-
129Phosphoserine.PSDNSGAEE
CCCCCCCCC
44.35UniProtKB
Link-
176PhosphotyrosineTGRYYAMKI
CCCEEEEEE
10.00Phosphositeplus
Link-
176Phosphotyrosine; by TNK2.TGRYYAMKI
CCCEEEEEE
10.00UniProtKB
Link-
224S-nitrosocysteineHDRLCFVME
CCEEEEEEE
2.23dbSNO
Link-
246PhosphoserineERVFSEDRA
CCCCCHHHH
35.41Phosphositeplus
Link-
296S-nitrosocysteineDFGLCKEGI
ECHHHHHHC
3.74dbSNO
Link-
305O-linked (GlcNAc)KDGATMKTF
CCCCEEEEE
25.40Phosphositeplus
Link-
305O-linked (GlcNAc...).KDGATMKTF
CCCCEEEEE
25.40UniProtKB
Link-
305PhosphothreonineKDGATMKTF
CCCCEEEEE
25.40Phosphositeplus
Link-
308DePhosphothreonineATMKTFCGT
CEEEEECCC
17.21HPRD
Link-
308PhosphothreonineATMKTFCGT
CEEEEECCC
17.21HPRD
Link-
308PhosphothreonineATMKTFCGT
CEEEEECCC
17.21HPRD
Link-
308PhosphothreonineATMKTFCGT
CEEEEECCC
17.21Phosphositeplus
Link-
308Phosphothreonine (CAMKK1)ATMKTFCGT
CEEEEECCC
17.21HPRD
Link-
308Phosphothreonine (PDK-1;PDK-1)ATMKTFCGT
CEEEEECCC
17.21PhosphoELM
Link-
308Phosphothreonine (PDK1)ATMKTFCGT
CEEEEECCC
17.21HPRD
Link-
308Phosphothreonine (PDPK1)ATMKTFCGT
CEEEEECCC
17.21HPRD
Link-
308Phosphothreonine; by PDPK1.ATMKTFCGT
CEEEEECCC
17.21UniProtKB
Link-
310S-nitrosocysteineMKTFCGTPE
EEEECCCHH
7.79dbSNO
Link-
312O-linked (GlcNAc)TFCGTPEYL
EECCCHHHC
17.71Phosphositeplus
Link-
312O-linked (GlcNAc...).TFCGTPEYL
EECCCHHHC
17.71UniProtKB
Link-
312PhosphothreonineTFCGTPEYL
EECCCHHHC
17.71Phosphositeplus
Link-
315PhosphotyrosineGTPEYLAPE
CCHHHCCHH
14.90Phosphositeplus
Link-
315Phosphotyrosine (SRC)GTPEYLAPE
CCHHHCCHH
14.90HPRD
Link-
326PhosphotyrosineEDNDYGRAV
CCCCCCCHH
18.11Phosphositeplus
Link-
326Phosphotyrosine (SRC)EDNDYGRAV
CCCCCCCHH
18.11HPRD
Link-
377Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)GPEAKSLLS
CHHHHHHHH
39.72Phosphositeplus
Link-
450PhosphothreonineMITITPPDQ
CCCCCCCCC
21.81HPRD
Link-
450PhosphothreonineMITITPPDQ
CCCCCCCCC
21.81PhosphoELM
Link-
450PhosphothreonineMITITPPDQ
CCCCCCCCC
21.81Phosphositeplus
Link-
462noneMECVDSERR
HHHHHCCCC
57.34HPRD
Link-
473DePhosphoserineFPQFSYSAS
HCCEEEECC
16.96HPRD
Link-
473PhosphoserineFPQFSYSAS
HCCEEEECC
16.96HPRD
Link-
473PhosphoserineFPQFSYSAS
HCCEEEECC
16.96HPRD
Link-
473PhosphoserineFPQFSYSAS
HCCEEEECC
16.96HPRD
Link-
473PhosphoserineFPQFSYSAS
HCCEEEECC
16.96Phosphositeplus
Link-
473Phosphoserine (ILK)FPQFSYSAS
HCCEEEECC
16.96HPRD
Link-
473Phosphoserine (PDK-1;ILK)FPQFSYSAS
HCCEEEECC
16.96PhosphoELM
Link-
473Phosphoserine (PDK1)FPQFSYSAS
HCCEEEECC
16.96HPRD
Link-
473Phosphoserine (PDPK1)FPQFSYSAS
HCCEEEECC
16.96HPRD
Link-
473Phosphoserine (RHEBL1)FPQFSYSAS
HCCEEEECC
16.96HPRD
Link-
473Phosphoserine; by MTOR.FPQFSYSAS
HCCEEEECC
16.96UniProtKB
Link-
474PhosphotyrosinePQFSYSASG
CCEEEECCC
15.00HPRD
Link-
474PhosphotyrosinePQFSYSASG
CCEEEECCC
15.00PhosphoELM
Link-
474PhosphotyrosinePQFSYSASG
CCEEEECCC
15.00Phosphositeplus
Link-
474Phosphotyrosine.PQFSYSASG
CCEEEECCC
15.00UniProtKB
Link-
475PhosphoserineQFSYSASGT
CEEEECCCC
18.11Phosphositeplus
Link-
477PhosphoserineSYSASGTA
EEECCCCC
30.64Phosphositeplus
Link-
479PhosphothreonineSASGTA
ECCCCC
27.05Phosphositeplus
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
O60593_HUMANphysical interactionMINT-61345MINT15784622
FRAP_HUMANphysical interactionMINT-16737MINT11438723
Q96EX0_HUMANphysical interactionMINT-61462MINT15784622
Q96EX0_HUMANphosphorylation reactionMINT-61479MINT15784622
Q96EX0_HUMANphysical interactionMINT-61466MINT15784622
Q96EX0_HUMANphysical interactionMINT-61467MINT15784622
Q96EX0_HUMANphysical interactionMINT-61468MINT15784622
Q96EX0_HUMANphysical interactionMINT-61346MINT15784622
AKT1_HUMANphysical interaction
physical interaction
EBI-296137
EBI-492734
intact7891724
7891724
Q7Z6J0_HUMANphosphorylationEBI-1374066
intact17535800
BCL10_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
EBI-958953
EBI-958972
EBI-958
intact16280327
16280327
16280327
16280327
GSK3B_HUMANphosphorylationEBI-963017
intact16282323
PEPL_HUMANphysical interactionEBI-368320
intact12244133
BRCA1_HUMANin vitro
in vivo
HPRD:01261HPRD10542266
CDN1A_HUMANin vitro
in vivo
HPRD:01261HPRD11756412
CREB1_HUMANin vitroHPRD:01261HPRD9829964
ESR1_HUMANin vitro
in vivo
HPRD:01261HPRD11139588
FOXO1_HUMANin vitro
in vivo
HPRD:01261HPRD10358014
NR4A1_HUMANin vitro
in vivo
HPRD:01261HPRD11274386
HS90A_HUMANin vivoHPRD:01261HPRD10995457
HD_HUMANin vitro
in vivo
HPRD:01261HPRD12062094
IMDH2_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:01261HPRD10930578
IRS1_HUMANin vivoHPRD:01261HPRD10497255
BRAF1_HUMANin vitro
in vivo
HPRD:01261HPRD10869359
11410590
RAF1_HUMANin vitro
in vivo
HPRD:01261HPRD10576742
MDM2_HUMANin vitro
in vivo
HPRD:01261HPRD12145204
11504915
F262_HUMANin vitroHPRD:01261HPRD12853467
ITB3_HUMANin vitroHPRD:01261HPRD10896934
PTN1_HUMANin vitro
in vivo
HPRD:01261HPRD11579209
TERT_HUMANin vitro
in vivo
HPRD:01261HPRD10224060
M3K8_HUMANin vivoHPRD:01261HPRD12138205
FOXO4_HUMANin vitro
in vivo
HPRD:01261HPRD11313479
10217147
11689711
16272144
BIRC4_HUMANin vitro
in vivo
HPRD:01261HPRD14645242
IRAK1_HUMANin vitro
in vivo
HPRD:01261HPRD11976320
ANDR_HUMANin vitro
in vivo
HPRD:01261HPRD11404460
11156376
16210317
M3K11_HUMANin vitro
in vivo
HPRD:01261HPRD12458207
IKKA_HUMANin vitro
in vivo
HPRD:01261HPRD10485710
CDN1B_HUMANin vitro
in vivo
HPRD:01261HPRD12244301
FRAP_HUMANin vitroHPRD:01261HPRD11438723
10910062
1433Z_HUMANin vitro
in vivo
HPRD:01261HPRD11956222
MP2K4_HUMANin vitro
in vivo
HPRD:01261HPRD11707464
ATX1_HUMANin vitro
in vivo
HPRD:01261HPRD12757707
12741986
PTEN_HUMANin vitro
in vivo
HPRD:01261HPRD12077256
10866658
12297295
EDG1_HUMANin vitro
in vivo
HPRD:01261HPRD11583630
PDE3B_HUMANin vitro
in vivo
HPRD:01261HPRD10454575
RAC1_HUMANin vitro
in vivo
HPRD:01261HPRD10617634
4EBP1_HUMANin vitroHPRD:01261HPRD11777913
CASP9_HUMANin vitroHPRD:01261HPRD9812896
M3K5_HUMANin vitro
in vivo
HPRD:01261HPRD11154276
FOXO3_HUMANin vitro
in vivo
HPRD:01261HPRD10102273
EP300_HUMANin vitroHPRD:01261HPRD11116148
CHK1_HUMANin vitroHPRD:01261HPRD12062056
BAD_HUMANin vitro
in vivo
HPRD:01261HPRD9381178
PEA15_HUMANin vitro
in vivo
HPRD:01261HPRD12808093
GAB2_HUMANin vitro
in vivo
HPRD:01261HPRD11782427
GSK3A_HUMANin vitro
in vivo
HPRD:01261HPRD11035810
11884598
8524413
FANCA_HUMANin vitroHPRD:01261HPRD11855836
TRMB_HUMANin vitroHPRD:01261HPRD15861136
YAP1_HUMANin vitro
in vivo
HPRD:01261HPRD12535517
AKTS1_HUMANin vitro
in vivo
HPRD:01261HPRD12524439
14973226
AHNK_HUMANin vitroHPRD:01261HPRD11535620
K1C10_HUMANin vivoHPRD:01261HPRD11585925
NOS3_HUMANin vitroHPRD:01261HPRD11696579
10376603
YBOX1_HUMANin vitro
in vivo
HPRD:01261HPRD16354698
TSC2_HUMANin vitroHPRD:01261HPRD12438239
12150915
GATA2_HUMANin vivoHPRD:01261HPRD15837948
HMOX1_HUMANin vitro
in vivo
HPRD:01261HPRD15581622
MDM4_HUMANin vitroHPRD:01261HPRD16163388
EZH2_HUMANin vitro
in vivo
HPRD:01261HPRD16224021
SH2B2_HUMANin vitro
in vivo
HPRD:01261HPRD16141217
APLP2_HUMANin vivoHPRD:01261HPRD10490823
AKT1_HUMANin vitroHPRD:01261HPRD7891724
9395488
GSK3B_HUMANin vitro
in vivo
HPRD:01261HPRD11035810
8524413
P85A_HUMANin vitroHPRD:01261HPRD10527852
RON_HUMANin vitroHPRD:01261HPRD12919677
STAT1_HUMANin vivoHPRD:01261HPRD15284024
PRKDC_HUMANin vitroHPRD:01261HPRD15262962
ESR2_HUMANin vivoHPRD:01261HPRD15001646
H2B2E_HUMANin vivoHPRD:01261HPRD9973250
PDK2_HUMANin vitroHPRD:01261HPRD10438924
PAK1_HUMANin vivoHPRD:01261HPRD12138087
IKKB_HUMANin vitro
in vivo
HPRD:01261HPRD10485711
DP13A_HUMANin vitro
in vivo
HPRD:01261HPRD12621049
RAB3D_HUMANin vitroHPRD:01261HPRD11903042
WNK1_HUMANin vitro
in vivo
HPRD:01261HPRD14611643
BIM_HUMANin vitro
in vivo
HPRD:01261HPRD16282323
RHG07_HUMANin vivo
yeast 2-hybrid
HPRD:01261HPRD16338927
GATA1_HUMANin vitro
in vivo
HPRD:01261HPRD16107690
PHB2_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:01261HPRD15173318
PDK2_HUMANENSP00000270202STRING
TCL1A_HUMANENSP00000270202STRING
PAR6A_HUMANENSP00000270202STRING
TSC2_HUMANENSP00000270202STRING
GSK3A_HUMANENSP00000270202STRING
KS6B1_HUMANENSP00000270202STRING
IL2_HUMANENSP00000270202STRING
CCND1_HUMANENSP00000270202STRING
PAXI_HUMANENSP00000270202STRING
CDN1B_HUMANENSP00000270202STRING
2A5D_HUMANENSP00000270202STRING
PP2AA_HUMANENSP00000270202STRING
CREB1_HUMANENSP00000270202STRING
JIP1_HUMANENSP00000270202STRING
ELAF_HUMANENSP00000270202STRING
CDN1A_HUMANENSP00000270202STRING
AHNK_HUMANENSP00000270202STRING
RAC2_HUMANENSP00000270202STRING
INS_HUMANENSP00000270202STRING
INS_HUMANENSP00000270202STRING
RAF1_HUMANENSP00000270202STRING
MDM2_HUMANENSP00000270202STRING
MP2K4_HUMANENSP00000270202STRING
MK03_HUMANENSP00000270202STRING
M3K8_HUMANENSP00000270202STRING
PK3CA_HUMANENSP00000270202STRING
FYV1_HUMANENSP00000270202STRING
EGF_HUMANENSP00000270202STRING
S2A4R_HUMANENSP00000270202STRING
RB_HUMANENSP00000270202STRING
ERBB2_HUMANENSP00000270202STRING
P85A_HUMANENSP00000270202STRING
RASA1_HUMANENSP00000270202STRING
CHK1_HUMANENSP00000270202STRING
DOCK1_HUMANENSP00000270202STRING
PDE3B_HUMANENSP00000270202STRING
PLXB1_HUMANENSP00000270202STRING
NOS3_HUMANENSP00000270202STRING
SHIP2_HUMANENSP00000270202STRING
ILK_HUMANENSP00000270202STRING
AKTIP_HUMANENSP00000270202STRING
GAB2_HUMANENSP00000270202STRING
BCLX_HUMANENSP00000270202STRING
IGF1B_HUMANENSP00000270202STRING
INSR_HUMANENSP00000270202STRING
IRS1_HUMANENSP00000270202STRING
BAD_HUMANENSP00000270202STRING
TERT_HUMANENSP00000270202STRING
KAPCA_HUMANENSP00000270202STRING
KAPCA_HUMANENSP00000270202STRING
M3K11_HUMANENSP00000270202STRING
CASP3_HUMANENSP00000270202STRING
TF65_HUMANENSP00000270202STRING
TF65_HUMANENSP00000270202STRING
CDC42_HUMANENSP00000270202STRING
BAIP2_HUMANENSP00000270202STRING
TRAF6_HUMANENSP00000270202STRING
VEGFA_HUMANENSP00000270202STRING
GTR4_HUMANENSP00000270202STRING
SP1_HUMANENSP00000270202STRING
COT2_HUMANENSP00000270202STRING
CASP9_HUMANENSP00000270202STRING
WT1_HUMANENSP00000270202STRING
HS90A_HUMANENSP00000270202STRING
HS90A_HUMANENSP00000270202STRING
HS90A_HUMANENSP00000270202STRING
HIF1A_HUMANENSP00000270202STRING
HIF1A_HUMANENSP00000270202STRING
IKKB_HUMANENSP00000270202STRING
FOXO3_HUMANENSP00000270202STRING
PEPL_HUMANENSP00000270202STRING
4EBP1_HUMANENSP00000270202STRING
ESR2_HUMANENSP00000270202STRING
PDPK1_HUMANENSP00000270202STRING
GLI2_HUMANENSP00000270202STRING
E2F1_HUMANENSP00000270202STRING
BIM_HUMANENSP00000270202STRING
M3K5_HUMANENSP00000270202STRING
PDE3A_HUMANENSP00000270202STRING
MK08_HUMANENSP00000270202STRING
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Disease Reference
Kegg disease
H00539 PTEN hamartoma tumor syndrome (PHTS), including: Cowden syndrome; Bannayan-Riley-Ruvalcaba syndrome;
OMIM disease
114480Breast cancer (BC)
114500Colorectal cancer (CRC)
Note=Genetic variations in AKT1 may play a role in susceptibility to ovarian cancer.
176920
615109Cowden syndrome 6 (CWS6)
Drug Reference
Kegg drug
D10381 Afuresertib (USAN)
D10382 Afuresertib hydrochloride (USAN)
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"The deacetylase SIRT1 promotes membrane localization and activationof Akt and PDK1 during tumorigenesis and cardiac hypertrophy.";
Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P.,Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P.;
Sci. Signal. 4:RA46-RA46(2011).
Cited for: INTERACTION WITH SIRT1, ACETYLATION AT LYS-14 AND LYS-20,DEACETYLATION AT LYS-14 AND LYS-20, AND MUTAGENESIS OF LYS-14; GLU-17AND LYS-20.
O-linked Glycosylation
ReferencePubMed
"Extensive crosstalk between O-GlcNAcylation and phosphorylationregulates Akt signaling.";
Wang S., Huang X., Sun D., Xin X., Pan Q., Peng S., Liang Z., Luo C.,Yang Y., Jiang H., Huang M., Chai W., Ding J., Geng M.;
PLoS ONE 7:E37427-E37427(2012).
Cited for: GLYCOSYLATION AT SER-126; SER-129; THR-305 AND THR-312.
Phosphorylation
ReferencePubMed
"Mechanism of activation of protein kinase B by insulin and IGF-1.";
Alessi D.R., Andjelkovic M., Caudwell F.B., Cron P., Morrice N.,Cohen P., Hemmings B.A.;
EMBO J. 15:6541-6551(1996).
Cited for: MUTAGENESIS OF THR-308 AND SER-473, AND PHOSPHORYLATION AT THR-308 ANDSER-473.
"Activation of protein kinase B beta and gamma isoforms by insulin invivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro:comparison with protein kinase B alpha.";
Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R.;
Biochem. J. 331:299-308(1998).
Cited for: FUNCTION, ENZYME REGULATION, AND PHOSPHORYLATION AT THR-308 BY PDPK1.
"Direct identification of tyrosine 474 as a regulatory phosphorylationsite for the Akt protein kinase.";
Conus N.M., Hannan K.M., Cristiano B.E., Hemmings B.A., Pearson R.B.;
J. Biol. Chem. 277:38021-38028(2002).
Cited for: PHOSPHORYLATION AT TYR-474, AND MUTAGENESIS OF TYR-474.
"PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Aktactivity and mediates cellular invasion.";
Ahn J.-Y., Rong R., Kroll T.G., Van Meir E.G., Snyder S.H., Ye K.;
J. Biol. Chem. 279:16441-16451(2004).
Cited for: INTERACTION WITH AGAP2, AND PHOSPHORYLATION AT SER-473.
"LGI1, a putative tumor metastasis suppressor gene, controls in vitroinvasiveness and expression of matrix metalloproteinases in gliomacells through the ERK1/2 pathway.";
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.;
J. Biol. Chem. 279:23151-23157(2004).
Cited for: PHOSPHORYLATION AT SER-473.
"Phosphorylation and regulation of Akt/PKB by the rictor-mTORcomplex.";
Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.;
Science 307:1098-1101(2005).
Cited for: PHOSPHORYLATION AT THR-308, AND PHOSPHORYLATION AT SER-473 BY MTOR.
"Activation of Akt independent of PTEN and CTMP tumor-suppressor genemutations in epilepsy-associated Taylor-type focal corticaldysplasias.";
Schick V., Majores M., Engels G., Spitoni S., Koch A., Elger C.E.,Simon M., Knobbe C., Bluemcke I., Becker A.J.;
Acta Neuropathol. 112:715-725(2006).
Cited for: PHOSPHORYLATION AT SER-473.
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-126 ANDSER-129, AND MASS SPECTROMETRY.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-126 ANDSER-129, AND MASS SPECTROMETRY.
"Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates itsactivation.";
Mahajan K., Coppola D., Challa S., Fang B., Chen Y.A., Zhu W.,Lopez A.S., Koomen J., Engelman R.W., Rivera C., Muraoka-Cook R.S.,Cheng J.Q., Schoenbrunn E., Sebti S.M., Earp H.S., Mahajan N.P.;
PLoS ONE 5:E9646-E9646(2010).
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308AND SER-473, MUTAGENESIS OF TYR-176, INTERACTION WITH TNK2, AND TISSUESPECIFICITY.
"Synthesis and structure based optimization of novel Akt inhibitors.";
Lippa B., Pan G., Corbett M., Li C., Kauffman G.S., Pandit J.,Robinson S., Wei L., Kozina E., Marr E.S., Borzillo G., Knauth E.,Barbacci-Tobin E.G., Vincent P., Troutman M., Baker D., Rajamohan F.,Kakar S., Clark T., Morris J.;
Bioorg. Med. Chem. Lett. 18:3359-3363(2008).
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 144-480, PHOSPHORYLATION ATTHR-308, AND ENZYME REGULATION.
"Design of selective, ATP-competitive inhibitors of Akt.";
Freeman-Cook K.D., Autry C., Borzillo G., Gordon D.,Barbacci-Tobin E., Bernardo V., Briere D., Clark T., Corbett M.,Jakubczak J., Kakar S., Knauth E., Lippa B., Luzzio M.J., Mansour M.,Martinelli G., Marx M., Nelson K., Pandit J., Rajamohan F.,Robinson S., Subramanyam C., Wei L., Wythes M., Morris J.;
J. Med. Chem. 53:4615-4622(2010).
Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 144-480, PHOSPHORYLATION ATTHR-308, AND ENZYME REGULATION.
"Phosphoinositide-3-OH kinase-dependent regulation of glycogensynthase kinase 3 and protein kinase B/AKT by the integrin-linkedkinase.";
Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.;
Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998).
Cited for: ENZYME REGULATION, AND PHOSPHORYLATION AT SER-473.
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