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Akt1 (human)

Overview Akt1 an oncogenic AGC kinase that plays a critical role in regulating cell survival and metabolism in many different signaling pathways. Dual phosphorylation is required for its activation. T308 is phosphorylated by PDK1 in the PI3 kinase pathway, and S473 is phosphorylated by mTOR in the mTORC2 pathway. The 'Lys-63'-linked ubiquitination of AKT1 by TRAF6 is important for its translocation to the plasma membrane, phosphorylation, and activation. When Akt is fully phosphorylated it translocates into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its proteosomal degradation. Hyperactive or overexpressed in a number of cancers including breast, prostate, lung, pancreatic, liver, ovarian and colorectal. Over 120 protein substrates are known including many that regulate transcription, metabolism, apoptosis, cell cycle, and growth. Note: This description may include information from UniProtKB. Protein type: Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); EC 2.7.11.1; Kinase, protein; AGC group; AKT family Cellular Component: microtubule cytoskeleton; nucleoplasm; lamellipodium; cytoplasm; plasma membrane; spindle; cytosol; nucleus Molecular Function: identical protein binding; protein serine/threonine kinase activity; protein binding; phosphatidylinositol-3,4,5-triphosphate binding; enzyme binding; protein kinase C binding; nitric-oxide synthase regulator activity; kinase activity; phosphatidylinositol-3,4-bisphosphate binding; ATP binding; protein kinase activity Biological Process: negative regulation of JNK cascade; positive regulation of nitric oxide biosynthetic process; nerve growth factor receptor signaling pathway; protein ubiquitination; glucose homeostasis; protein amino acid phosphorylation; G1/S-specific positive regulation of cyclin-dependent protein kinase activity; regulation of cell migration; germ cell development; positive regulation of glucose import; cell projection organization and biogenesis; protein catabolic process; maternal placenta development; response to food; platelet activation; glycogen biosynthetic process; fibroblast growth factor receptor signaling pathway; positive regulation of nitric-oxide synthase activity; positive regulation of blood vessel endothelial cell migration; glucose metabolic process; positive regulation of lipid biosynthetic process; positive regulation of cell growth; mRNA metabolic process; cellular response to insulin stimulus; insulin-like growth factor receptor signaling pathway; response to heat; T cell costimulation; positive regulation of fat cell differentiation; negative regulation of protein kinase activity; striated muscle cell differentiation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription factor activity; regulation of nitric-oxide synthase activity; anagen; negative regulation of apoptosis; negative regulation of fatty acid beta-oxidation; translation; apoptosis; protein amino acid autophosphorylation; positive regulation of cellular protein metabolic process; positive regulation of glycogen biosynthetic process; regulation of glycogen biosynthetic process; negative regulation of cell size; negative regulation of caspase activity; glucose transport; signal transduction; nitric oxide metabolic process; regulation of translation; apoptotic mitochondrial changes; RNA metabolic process; protein kinase B signaling cascade; nitric oxide biosynthetic process; inflammatory response; cell differentiation; activated T cell apoptosis; epidermal growth factor receptor signaling pathway; phosphoinositide-mediated signaling; myelin maintenance in the peripheral nervous system; protein modification process; endocrine pancreas development; positive regulation of peptidyl-serine phosphorylation; osteoblast differentiation; cell proliferation; G-protein coupled receptor protein signaling pathway; peptidyl-serine phosphorylation; protein import into nucleus, translocation; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; insulin receptor signaling pathway; gene expression; positive regulation of protein amino acid phosphorylation; blood coagulation; phosphorylation Reference #:  P31749 (UniProtKB) Alt. Names/Synonyms: AKT; AKT1; AKT1 kinase; MGC99656; PKB; PKB-ALPHA; PRKBA; Protein kinase B; Proto-oncogene c-Akt; RAC; rac protein kinase alpha; RAC-ALPHA; RAC-alpha serine/threonine-protein kinase; RAC-PK-alpha; v-akt murine thymoma viral oncogene homolog 1 Gene Symbols: AKT1 Molecular weight: 55,686 Da Basal Isoelectric point: 5.75  Predict pI for various phosphorylation states CST Pathways:  Adherens Junction Dynamics  |  Alzheimer's Disease  |  AMPK Signaling  |  Angiogenesis  |  Apoptosis  |  B Cell Receptor Signaling  |  Cell Cycle: G1/S Checkpoint  |  ErbB/HER Signaling  |  ESC Pluripotency and Differentiation  |  Inhibition of Apoptosis  |  Jak/Stat/IL-6 Signaling  |  Mitochondrial Control of Apoptosis  |  mTOR Signaling  |  NF-kB Signaling  |  PI3K/Akt Signaling  |  Protein Kinase C Signaling  |  Regulation of Microtubule Dynamics  |  T Cell Receptor Signaling  |  TGF-ß Signaling  |  Translation: eIF4E and p70S6K  |  Warburg Effect Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below Akt1 1H10 - A=1-123 (human) 1UNP - A=1-121 (human) 1UNQ - A=1-123 (human) 1UNR - A=1-123 (human) 2UVM - A=1-123 (human) 2UZR - A=1-123 (human) 2UZS - A=1-123 (human) 3CQU - A=144-480 (human) 3CQW - A=144-480 (human) 3MV5 - A=144-480 (human) 3MVH - A=144-480 (human) 3O96 - A=2-443 (human) 3OCB - A/B=144-480 (human) 3OW4 - A/B=144-480 (human) 3QKK - A=144-480 (human) 3QKL - A=144-480 (human) 3QKM - A=144-480 (human) 4EJN - A=2-446 (human) 4EKK - A/B=144-480 (human) 4EKL - A=144-480 (human) 4GV1 - A=144-480 (human) Substrate Sequence Logo

STRING  |  Scansite  |  KinBase  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB 1H10 1UNP 1UNQ 1UNR 2UVM 2UZR 2UZS 3CQU 3CQW 3MV5 3MVH 3O96 3OCB 3OW4 3QKK 3QKL 3QKM 4EJN 4EKK 4EKL 4GV1  |  ENZYME  |  Phospho3D  |  DISEASE 114480 114500 164730 181500 604370  |  Source  |  NURSA  |  InnateDB  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein

	Sites Implicated In
apoptosis, altered: T308, S473 apoptosis, induced: T450 apoptosis, inhibited: T72, S129, S246, T308, S473 carcinogenesis, altered: S473 carcinogenesis, induced: T308, S473 cell cycle regulation: Y176, T308, S473 cell differentiation, altered: T450, S473 cell growth, altered: T308, S473 cell motility, altered: T308, S473 cytoskeletal reorganization: T308, S473 transcription, altered: Y176, T308, Y315, T450, S473 transcription, induced: S129 translation, altered: T450 activation: T308, T450, S473 enzymatic activity, induced: K8, K14, T72, S124, S129, Y176, S246, T308, Y315, Y326, T450, S473, Y474 enzymatic activity, inhibited: T305, T312, T450 intracellular localization: K8, K14, Y176, T308, S473 molecular association, regulation: T308, S473 phosphorylation: K8, K14, T305, T308, T312, S473 protein conformation: T308, T450 protein degradation: S473 ubiquitination: T450

	Modification Sites and Domains
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	Modification Sites in Parent Protein, Orthologs, and Isoforms

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
1	0		T34	FLLKNDGTFIGYKER
0	1		T65	AQCQLMKtERPRPNt
1	0		T72	tERPRPNtFIIRCLQ
0	1		T87	WTTVIERtFHVEtPE
0	1		T92	ERtFHVEtPEEREEW
0	1		E117	LKKQEEEEMDFRsGs
0	6		S122	EEEMDFRsGsPsDNs
4	5		S124	EMDFRsGsPsDNsGA
0	9		S126	DFRsGsPsDNsGAEE
5	17		S129	sGsPsDNsGAEEMEV
0	1		S137	GAEEMEVSLAKPKHR
0	9		T146	AKPKHRVtMNEFEYL
1	1		Y176	EKATGRYyAMKILKK
1	0		S246	LSRERVFsEDRARFY
0	6		T305	EGIKDGAtMKtFCGt
448	13		T308	KDGAtMKtFCGtPEy
0	2		T312	tMKtFCGtPEyLAPE
4	13		Y315	tFCGtPEyLAPEVLE
3	26		Y326	EVLEDNDyGRAVDWW
0	2		Y417	GIVWQHVyEKKLSPP
0	3		Y437	TSETDTRyFDEEFTA
18	1		T450	TAQMITItPPDQDDS
1119	49		S473	RPHFPQFsysAsGtA
1	14		Y474	PHFPQFsysAsGtA_
0	3		S475	HFPQFsysAsGtA__
1	3		S477	PQFsysAsGtA____
0	10		T479	FsysAsGtA______

	mouse
T34	FLLKNDGTFIGYKER
T65	AQCQLMKTERPRPNT
T72	TERPRPNTFIIRCLQ
T87	WTTVIERTFHVETPE
T92	ERTFHVETPEEREEW
T117	LKRQEEEtMDFRsGs
S122	EEtMDFRsGsPsDNs
S124	tMDFRsGsPsDNsGA
S126	DFRsGsPsDNsGAEE
S129	sGsPsDNsGAEEMEV
S137	GAEEMEVsLAKPKHR
T146	AKPKHRVTMNEFEYL
Y176	EKATGRYyAMKILKK
S246	LSRERVFSEDRARFY
T305	EGIKDGAtMKtFCGt
T308	KDGAtMKtFCGtPEy
T312	tMKtFCGtPEyLAPE
Y315	tFCGtPEyLAPEVLE
Y326	EVLEDNDyGRAVDWW
Y417	NIVWQDVYEKKLSPP
Y437	TSETDTRYFDEEFTA
T450	TAQMITItPPDQDDS
S473	RPHFPQFsysASGtA
Y474	PHFPQFsysASGtA_
S475	HFPQFsysASGtA__
S477	PQFsysASGtA____
T479	FsysASGtA______

	rat
T34	FLLKNDGtFIGYKER
T65	AQCQLMKTERPRPNT
T72	TERPRPNTFIIRCLQ
T87	WTTVIERTFHVETPE
T92	ERTFHVETPEEREEW
T117	LKRQEEETMDFRSGs
S122	EETMDFRSGsPSDNS
S124	TMDFRSGsPSDNSGA
S126	DFRSGsPSDNSGAEE
S129	SGsPSDNSGAEEMEV
A137	GAEEMEVALAKPKHR
T146	AKPKHRVTMNEFEYL
Y176	EKATGRYYAMKILKK
S246	LSRERVFSEDRARFY
T305	EGIKDGATMKtFCGT
T308	KDGATMKtFCGTPEY
T312	TMKtFCGTPEYLAPE
Y315	tFCGTPEYLAPEVLE
Y326	EVLEDNDYGRAVDWW
Y417	NIVWQDVYEKKLSPP
Y437	TSETDTRYFDEEFTA
T450	TAQMITItPPDQDDS
S473	RPHFPQFsYSASGTA
Y474	PHFPQFsYSASGTA_
S475	HFPQFsYSASGTA__
S477	PQFsYSASGTA____
T479	FsYSASGTA______

	fruit fly
R135	FVLHSDGRLMGYRSK
T167	VRGCQIMTVDRPKPF
T175	VDRPKPFTFIIRGLQ
T190	WTTVIERTFAVESEL
S195	ERTFAVESELERQQW
M229	TPSEQTDMTDVDMAT
M234	TDMTDVDMATIAEDE
T236	MTDVDMATIAEDELS
A238	DVDMATIAEDELSEQ
E241	MATIAEDELSEQFSV
-	gap
T262	SSGVKKVTLENFEFL
Y292	EKATAKLYAIKILKK
T362	LSHERIFTEDRTRFY
T420	EDITYGRTTKTFCGT
T423	TYGRTTKTFCGTPEY
T427	TTKTFCGTPEYLAPE
Y430	TFCGTPEYLAPEVLD
Y441	EVLDDNDYGQAVDWW
V532	SINWTDLVLKKIPPP
Y552	TSDTDTRYFDKEFTG
T565	TGESVELTPPDPTGP
S586	EPLFPQFSYQGDMAS
Y587	PLFPQFSYQGDMAST
Q588	LFPQFSYQGDMASTL
T603	GTSSHISTSTSLASM
T605	SSHISTSTSLASMQ_

	cow
T34	FLLKNDGTFIGYKER
T65	AQCQLMKTERPRPNT
T72	TERPRPNTFIIRCLQ
T87	WTTVIERTFHVETPE
T92	ERTFHVETPEEREEW
T117	LKRQEEETMDFRSGS
S122	EETMDFRSGSPGENS
S124	TMDFRSGSPGENSGA
G126	DFRSGSPGENSGAEE
S129	SGSPGENSGAEEMEV
S137	GAEEMEVSLAKPKHR
T146	AKPKHRVTMNDFEYL
Y176	EKATGRYYAMKILKK
S246	LSRERVFSEDRARFY
T305	EGIKDGATMKtFCGT
T308	KDGATMKtFCGTPEY
T312	TMKtFCGTPEYLAPE
Y315	tFCGTPEYLAPEVLE
Y326	EVLEDNDYGRAVDWW
Y417	SIVWQDVYEKKLSPP
Y437	TSETDTRYFDEEFTA
T450	TAQMITITPPDQDDS
S473	RPHFPQFsYSASATA
Y474	PHFPQFsYSASATA_
S475	HFPQFsYSASATA__
S477	PQFsYSASATA____
T479	FsYSASATA______

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