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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: Kinase, protein; Protein kinase, AGC; EC 2.7.11.1; Protein kinase, Ser/Thr (non-receptor); AGC group; AKT family Cellular Component: microtubule cytoskeleton; nucleoplasm; lamellipodium; cytoplasm; plasma membrane; spindle; cytosol; nucleus Molecular Function: protein serine/threonine kinase activity; identical protein binding; protein binding; enzyme binding; phosphatidylinositol-3,4,5-triphosphate 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; G1/S-specific positive regulation of cyclin-dependent protein kinase activity; regulation of cell migration; protein amino acid phosphorylation; 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; insulin-like growth factor receptor signaling pathway; cellular response to insulin stimulus; response to heat; T cell costimulation; positive regulation of fat cell differentiation; striated muscle cell differentiation; negative regulation of protein kinase activity; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; regulation of nitric-oxide synthase activity; anagen; negative regulation of apoptosis; negative regulation of fatty acid beta-oxidation; translation; apoptosis; protein amino acid autophosphorylation; regulation of glycogen biosynthetic process; positive regulation of glycogen biosynthetic process; positive regulation of cellular protein metabolic 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; inflammatory response; cell differentiation; nitric oxide biosynthetic process; 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‑p, S473‑p apoptosis, induced: T450‑p apoptosis, inhibited: T72‑p, S129‑p, S246‑p, T308‑p, S473‑p carcinogenesis, altered: S473‑p carcinogenesis, induced: T308‑p, S473‑p cell cycle regulation: Y176‑p, T308‑p, S473‑p cell differentiation, altered: T450‑p, S473‑p cell growth, altered: T308‑p, S473‑p cell motility, altered: T308‑p, S473‑p cytoskeletal reorganization: T308‑p, S473‑p transcription, altered: Y176‑p, T308‑p, Y315‑p, T450‑p, S473‑p transcription, induced: S129‑p translation, altered: T450‑p activation: T308‑p, T450‑p, S473‑p enzymatic activity, induced: K8‑u, K14‑u, T72‑p, S124‑p, S129‑p, Y176‑p, S246‑p, T308‑p, Y315‑p, Y326‑p, T450‑p, S473‑p, Y474‑p enzymatic activity, inhibited: T305‑gl, T312‑gl, T450‑p intracellular localization: K8‑u, K14‑u, Y176‑p, T308‑p, S473‑p molecular association, regulation: T308‑p, S473‑p phosphorylation: K8‑u, K14‑u, T305‑gl, T308‑p, T312‑gl, S473‑p protein conformation: T308‑p, T450‑p protein degradation: S473‑p ubiquitination: T450‑p

	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

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	1		K8-u	MSDVAIVkEGWLHkR
1	0		K14-u	VkEGWLHkRGEYIKT
0	2		K30-u	RPRYFLLkNDGTFIG
1	0		T34	FLLkNDGTFIGYKER
0	1		T65-p	AQCQLMKtERPRPNt
1	0		T72-p	tERPRPNtFIIRCLQ
0	1		T87-p	WTTVIERtFHVEtPE
0	1		T92-p	ERtFHVEtPEEREEW
0	1		E117	LKKQEEEEMDFRsGs
0	6		S122-p	EEEMDFRsGsPsDNs
4	5		S124-p	EMDFRsGsPsDNsGA
0	1		S126-gl	DFRsGsPsDNsGAEE
0	9		S126-p	DFRsGsPsDNsGAEE
0	1		S129-gl	sGsPsDNsGAEEMEV
5	17		S129-p	sGsPsDNsGAEEMEV
0	1		S137	GAEEMEVSLAKPKHR
0	9		T146-p	AKPKHRVtMNEFEYL
1	1		Y176-p	EKATGRYyAMKILKK
1	0		S246-p	LSRERVFsEDRARFY
0	2		K276-u	NVVYRDLkLENLMLD
1	1		T305-gl	EGIKDGAtMKtFCGt
0	6		T305-p	EGIKDGAtMKtFCGt
448	13		T308-p	KDGAtMKtFCGtPEy
1	1		T312-gl	tMKtFCGtPEyLAPE
0	2		T312-p	tMKtFCGtPEyLAPE
4	13		Y315-p	tFCGtPEyLAPEVLE
3	26		Y326-p	EVLEDNDyGRAVDWW
0	2		K377-u	RTLGPEAkSLLSGLL
0	2		Y417-p	GIVWQHVyEKkLSPP
0	1		K420-a	WQHVyEKkLSPPFkP
0	1		K426-a	KkLSPPFkPQVTSET
0	3		Y437-p	TSETDTRyFDEEFTA
18	1		T450-p	TAQMITItPPDQDDS
1119	49		S473-p	RPHFPQFsysAsGtA
2	0		S473	RPHFPQFSysAsGtA
1	14		Y474-p	PHFPQFsysAsGtA_
0	3		S475-p	HFPQFsysAsGtA__
1	3		S477-p	PQFsysAsGtA____
0	10		T479-p	FsysAsGtA______

	mouse
K8	MNDVAIVKEGWLHKR
K14	VKEGWLHKRGEYIKT
K30-u	RPRYFLLkNDGTFIG
T34	FLLkNDGTFIGYKER
T65	AQCQLMKTERPRPNT
T72	TERPRPNTFIIRCLQ
T87	WTTVIERTFHVETPE
T92	ERTFHVETPEEREEW
T117-p	LKRQEEEtMDFRsGs
S122-p	EEtMDFRsGsPsDNs
S124-p	tMDFRsGsPsDNsGA
S126	DFRsGsPSDNsGAEE
S126-p	DFRsGsPsDNsGAEE
S129	sGsPsDNSGAEEMEV
S129-p	sGsPsDNsGAEEMEV
S137-p	GAEEMEVsLAKPKHR
T146	AKPKHRVTMNEFEYL
Y176-p	EKATGRYyAMKILKK
S246	LSRERVFSEDRARFY
K276-u	NVVYRDLkLENLMLD
T305	EGIKDGATMKtFCGt
T305-p	EGIKDGAtMKtFCGt
T308-p	KDGAtMKtFCGtPEy
T312	tMKtFCGTPEyLAPE
T312-p	tMKtFCGtPEyLAPE
Y315-p	tFCGtPEyLAPEVLE
Y326-p	EVLEDNDyGRAVDWW
K377	RTLGPEAKSLLSGLL
Y417	NIVWQDVYEKKLSPP
K420	WQDVYEKKLSPPFKP
K426	KKLSPPFKPQVTSET
Y437	TSETDTRYFDEEFTA
T450-p	TAQMITItPPDQDDS
S473-p	RPHFPQFsysASGtA
S473-gl	RPHFPQFsysASGtA
Y474-p	PHFPQFsysASGtA_
S475-p	HFPQFsysASGtA__
S477	PQFsysASGtA____
T479-p	FsysASGtA______

	rat
K8	MNDVAIVKEGWLHKR
K14	VKEGWLHKRGEYIKT
K30	RPRYFLLKNDGtFIG
T34-p	FLLKNDGtFIGYKER
T65	AQCQLMKTERPRPNT
T72	TERPRPNTFIIRCLQ
T87	WTTVIERTFHVETPE
T92	ERTFHVETPEEREEW
T117	LKRQEEETMDFRSGs
S122	EETMDFRSGsPSDNS
S124-p	TMDFRSGsPSDNSGA
S126	DFRSGsPSDNSGAEE
S126	DFRSGsPSDNSGAEE
S129	SGsPSDNSGAEEMEV
S129	SGsPSDNSGAEEMEV
A137	GAEEMEVALAKPKHR
T146	AKPKHRVTMNEFEYL
Y176	EKATGRYYAMKILKK
S246	LSRERVFSEDRARFY
K276	NVVYRDLKLENLMLD
T305	EGIKDGATMKtFCGT
T305	EGIKDGATMKtFCGT
T308-p	KDGATMKtFCGTPEY
T312	TMKtFCGTPEYLAPE
T312	TMKtFCGTPEYLAPE
Y315	tFCGTPEYLAPEVLE
Y326	EVLEDNDYGRAVDWW
K377	RTLGPEAKSLLSGLL
Y417	NIVWQDVYEKKLSPP
K420	WQDVYEKKLSPPFKP
K426	KKLSPPFKPQVTSET
Y437	TSETDTRYFDEEFTA
T450-p	TAQMITItPPDQDDS
S473-p	RPHFPQFsYSASGTA
S473-gl	RPHFPQFsYSASGTA
Y474	PHFPQFsYSASGTA_
S475	HFPQFsYSASGTA__
S477	PQFsYSASGTA____
T479	FsYSASGTA______

	fruit fly
K109	TEQTQVVKEGWLMKR
K115	VKEGWLMKRGEHIKN
H131	RQRYFVLHSDGRLMG
R135	FVLHSDGRLMGYRSK
T167	VRGCQIMTVDRPKPF
T175	VDRPKPFTFIIRGLQ
T190	WTTVIERTFAVESEL
S195	ERTFAVESELERQQW
M229	TPSEQTDMTDVDMAT
M234	TDMTDVDMATIAEDE
T236	MTDVDMATIAEDELS
A238	DVDMATIAEDELSEQ
A238	DVDMATIAEDELSEQ
E241	MATIAEDELSEQFSV
E241	MATIAEDELSEQFSV
-	gap
T262	SSGVKKVTLENFEFL
Y292	EKATAKLYAIKILKK
T362	LSHERIFTEDRTRFY
K391	GIIYRDLKLENLLLD
T420	EDITYGRTTKTFCGT
T420	EDITYGRTTKTFCGT
T423	TYGRTTKTFCGTPEY
T427	TTKTFCGTPEYLAPE
T427	TTKTFCGTPEYLAPE
Y430	TFCGTPEYLAPEVLD
Y441	EVLDDNDYGQAVDWW
K492	RNITDEAKNLLAGLL
V532	SINWTDLVLKKIPPP
K535	WTDLVLKKIPPPFKP
K541	KKIPPPFKPQVTSDT
Y552	TSDTDTRYFDKEFTG
T565	TGESVELTPPDPTGP
S586	EPLFPQFSYQGDMAS
S586	EPLFPQFSYQGDMAS
Y587	PLFPQFSYQGDMAST
Q588	LFPQFSYQGDMASTL
T603	GTSSHISTSTSLASM
T605	SSHISTSTSLASMQ_

	cow
K8	MNDVAIVKEGWLHKR
K14	VKEGWLHKRGEYIKT
K30	RPRYFLLKNDGTFIG
T34	FLLKNDGTFIGYKER
T65	AQCQLMKTERPRPNT
T72	TERPRPNTFIIRCLQ
T87	WTTVIERTFHVETPE
T92	ERTFHVETPEEREEW
T117	LKRQEEETMDFRSGS
S122	EETMDFRSGSPGENS
S124	TMDFRSGSPGENSGA
G126	DFRSGSPGENSGAEE
G126	DFRSGSPGENSGAEE
S129	SGSPGENSGAEEMEV
S129	SGSPGENSGAEEMEV
S137	GAEEMEVSLAKPKHR
T146	AKPKHRVTMNDFEYL
Y176	EKATGRYYAMKILKK
S246	LSRERVFSEDRARFY
K276	EVVYRDLKLENLMLD
T305	EGIKDGATMKtFCGT
T305	EGIKDGATMKtFCGT
T308-p	KDGATMKtFCGTPEY
T312	TMKtFCGTPEYLAPE
T312	TMKtFCGTPEYLAPE
Y315	tFCGTPEYLAPEVLE
Y326	EVLEDNDYGRAVDWW
K377	RTLSPEAKSLLSGLL
Y417	SIVWQDVYEKKLSPP
K420	WQDVYEKKLSPPFKP
K426	KKLSPPFKPQVTSET
Y437	TSETDTRYFDEEFTA
T450	TAQMITITPPDQDDS
S473-p	RPHFPQFsYSASATA
S473	RPHFPQFSYSASATA
Y474	PHFPQFsYSASATA_
S475	HFPQFsYSASATA__
S477	PQFsYSASATA____
T479	FsYSASATA______

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