AKT1 (AKT serine/threonine kinase 1)

Gene

• Entrez ID: 207
• Gene name: AKT serine/threonine kinase 1
• Gene symbol: AKT1
• Synonyms: AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA
• Chromosome: 14
• Chromosome location: 14q32.33
• Summary: This gene encodes one of the three members of the human AKT serine-threonine protein kinase family which are often referred to as protein kinase B alpha, beta, and gamma. These highly similar AKT proteins all have an N-terminal pleckstrin homology domain, a serine/threonine-specific kinase domain and a C-terminal regulatory domain. These proteins are phosphorylated by phosphoinositide 3-kinase (PI3K). AKT/PI3K forms a key component of many signalling pathways that involve the binding of membrane-bound ligands such as receptor tyrosine kinases, G-protein coupled receptors, and integrin-linked kinase. These AKT proteins therefore regulate a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. AKT proteins are recruited to the cell membrane by phosphatidylinositol 3,4,5-trisphosphate (PIP3) after phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) by PI3K. Subsequent phosphorylation of both threonine residue 308 and serine residue 473 is required for full activation of the AKT1 protein encoded by this gene. Phosphorylation of additional residues also occurs, for example, in response to insulin growth factor-1 and epidermal growth factor. Protein phosphatases act as negative regulators of AKT proteins by dephosphorylating AKT or PIP3. The PI3K/AKT signalling pathway is crucial for tumor cell survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating AKT1 which then phosphorylates and inactivates components of the apoptotic machinery. AKT proteins also participate in the mammalian target of rapamycin (mTOR) signalling pathway which controls the assembly of the eukaryotic translation initiation factor 4F (eIF4E) complex and this pathway, in addition to responding to extracellular signals from growth factors and cytokines, is disregulated in many cancers. Mutations in this gene are associated with multiple types of cancer and excessive tissue growth including Proteus syndrome and Cowden syndrome 6, and breast, colorectal, and ovarian cancers. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121434592	C>T	Pathogenic, likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, non coding transcript variant
rs368667384	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, non coding transcript variant
rs397514644	G>A	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs397514645	T>G	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057518602	T>C	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1057519804	G>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1595251483	TC>CT	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003984	hsa-miR-199a-3p	Western blot	18456660
MIRT004363	hsa-miR-125b-5p	qRT-PCR, Western blot	18649363
MIRT004701	hsa-miR-185-5p	Flow, Immunoblot, Microarray, qRT-PCR	19688090
MIRT005355	hsa-miR-149-3p	Luciferase reporter assay, qRT-PCR, Western blot, Reporter assay;Western blot;qRT-PCR;Other	20623644
MIRT005740	hsa-miR-451a	qRT-PCR, Western blot	20816946
MIRT007171	hsa-miR-302a-3p	Luciferase reporter assay	23185040
MIRT007172	hsa-miR-302b-3p	Luciferase reporter assay	23185040
MIRT007173	hsa-miR-302c-3p	Luciferase reporter assay	23185040
MIRT007174	hsa-miR-302d-3p	Luciferase reporter assay	23185040
MIRT007179	hsa-miR-143-3p	Luciferase reporter assay, qRT-PCR, Western blot	23104321
MIRT029530	hsa-miR-26b-5p	Microarray	19088304
MIRT041236	hsa-miR-193b-3p	CLASH	23622248
MIRT053334	hsa-miR-100-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23724047
MIRT054156	hsa-miR-19a-3p	qRT-PCR, Western blot	25400827
MIRT054156	hsa-miR-19a-3p	qRT-PCR, Western blot	25914465
MIRT054875	hsa-miR-133b	Luciferase reporter assay, qRT-PCR, Western blot	25414595
MIRT277753	hsa-miR-542-3p	Immunohistochemistry, Luciferase reporter assay, Western blot	26286747
MIRT437386	hsa-miR-708-5p	Flow, qRT-PCR, Western blot	23754151
MIRT437912	hsa-miR-105-5p	Luciferase reporter assay, Western blot	25280563
MIRT438059	hsa-miR-27a-5p	In situ hybridization, qRT-PCR	23963114
MIRT442863	hsa-miR-192-3p	PAR-CLIP	22100165
MIRT442864	hsa-miR-155-5p	PAR-CLIP	22100165
MIRT442865	hsa-miR-496	PAR-CLIP	22100165
MIRT442866	hsa-miR-4742-3p	PAR-CLIP	22100165
MIRT442867	hsa-miR-654-3p	PAR-CLIP	22100165
MIRT442868	hsa-miR-4757-3p	PAR-CLIP	22100165
MIRT442869	hsa-miR-365b-3p	PAR-CLIP	22100165
MIRT442870	hsa-miR-365a-3p	PAR-CLIP	22100165
MIRT543134	hsa-miR-3191-5p	PAR-CLIP	21572407
MIRT543135	hsa-miR-6873-3p	PAR-CLIP	21572407
MIRT543136	hsa-miR-6503-3p	PAR-CLIP	21572407
MIRT543137	hsa-miR-422a	PAR-CLIP	21572407
MIRT543138	hsa-miR-378i	PAR-CLIP	21572407
MIRT543139	hsa-miR-378h	PAR-CLIP	21572407
MIRT543140	hsa-miR-378f	PAR-CLIP	21572407
MIRT543141	hsa-miR-378e	PAR-CLIP	21572407
MIRT543142	hsa-miR-378d	PAR-CLIP	21572407
MIRT543143	hsa-miR-378c	PAR-CLIP	21572407
MIRT543144	hsa-miR-378b	PAR-CLIP	21572407
MIRT543145	hsa-miR-378a-3p	PAR-CLIP	21572407
MIRT543146	hsa-miR-4638-3p	PAR-CLIP	21572407
MIRT543147	hsa-miR-6824-3p	PAR-CLIP	21572407
MIRT543148	hsa-miR-6764-3p	PAR-CLIP	21572407
MIRT543149	hsa-miR-330-5p	PAR-CLIP	21572407
MIRT543150	hsa-miR-326	PAR-CLIP	21572407
MIRT543151	hsa-miR-6817-3p	PAR-CLIP	21572407
MIRT543152	hsa-miR-518c-5p	PAR-CLIP	21572407
MIRT543153	hsa-miR-7110-3p	PAR-CLIP	21572407
MIRT543154	hsa-miR-6866-3p	PAR-CLIP	21572407
MIRT543155	hsa-miR-188-5p	PAR-CLIP	21572407
MIRT543156	hsa-miR-625-3p	PAR-CLIP	21572407
MIRT731064	hsa-miR-99a-5p	Luciferase reporter assay	25187230
MIRT731064	hsa-miR-99a-5p	Luciferase reporter assay	27158364
MIRT731198	hsa-miR-637	Immunohistochemistry, In situ hybridization, Western blot, Luciferase reporter assay	25597410
MIRT731805	hsa-miR-495-3p	Luciferase reporter assay, qRT-PCR, Western blot	27323412
MIRT732839	hsa-miR-138-5p	Immunohistochemistry, Luciferase reporter assay, Western blot	28122142
MIRT733060	hsa-miR-184	Luciferase reporter assay	27666871
MIRT733141	hsa-miR-196b-5p	Flow, qRT-PCR, Western blot	26998071
MIRT733152	hsa-miR-34a-5p	Flow, qRT-PCR, Western blot	27073535
MIRT733440	hsa-miR-206	qRT-PCR, Western blot	28386239
MIRT733532	hsa-miR-409-3p	Luciferase reporter assay, qRT-PCR, Western blot	26631969
MIRT733740	hsa-miR-340-5p	Western blot	28057912
MIRT734052	hsa-miR-22-3p	Luciferase reporter assay, Western blot	26364720
MIRT734063	hsa-miR-192-5p	Western blot	26351877
MIRT734302	hsa-miR-125a-5p	qRT-PCR, Western blot	26622553
MIRT734751	hsa-miR-494-3p	Immunofluorescence, Immunohistochemistry, qRT-PCR, Western blot	25662849
MIRT734872	hsa-miR-4689	Luciferase reporter assay, qRT-PCR	25756961
MIRT735321	hsa-miR-374b-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	26100275
MIRT735357	hsa-miR-185-3p	Luciferase reporter assayMTT	26617940
MIRT735362	hsa-miR-10b-5p	qRT-PCR, Western blot	27347488
MIRT735413	hsa-miR-382-3p	qRT-PCR, Western blot, Immunostaining	26636539
MIRT735543	hsa-miR-126-3p	qRT-PCR, Western blot	26659078

Transcription factors

Transcription factor	Regulation	Reference
APC	Repression	15888491
AR	Activation	11278645
AR	Repression	20589722
GLI1	Unknown	23580656
NFKB1	Repression	18031796
RELA	Repression	18031796
STAT3	Unknown	16007214
TP53	Repression	12485897

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001649	Process	Osteoblast differentiation	IEA
GO:0001893	Process	Maternal placenta development	IEA
GO:0001934	Process	Positive regulation of protein phosphorylation	IDA	19057511
GO:0001938	Process	Positive regulation of endothelial cell proliferation	IMP	19850054
GO:0002042	Process	Cell migration involved in sprouting angiogenesis	IMP	28341552
GO:0003376	Process	Sphingosine-1-phosphate receptor signaling pathway	IMP	18558630
GO:0004672	Function	Protein kinase activity	TAS	10570282
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	17030608
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	10102273, 10983986, 11994271, 16139227, 16540465, 19667065, 32322062
GO:0004674	Function	Protein serine/threonine kinase activity	NAS	28386764
GO:0004674	Function	Protein serine/threonine kinase activity	TAS	21432781, 21711983
GO:0004712	Function	Protein serine/threonine/tyrosine kinase activity	IDA	22797923
GO:0005080	Function	Protein kinase C binding	IEA
GO:0005515	Function	Protein binding	IPI	10102273, 10983986, 11154276, 11438723, 11839802, 12176997, 12244133, 12791994, 16044149, 16139227, 16280327, 16282323, 16417524, 16525023, 16537421, 16792529, 17006541, 17577629, 17932490, 18191226, 18250332, 18292230, 18505846, 18562279, 18624398, 18650932, 18786403, 19162005, 191
GO:0005516	Function	Calmodulin binding	IDA	29104511
GO:0005524	Function	ATP binding	IC	11994271
GO:0005524	Function	ATP binding	IDA	16540465
GO:0005547	Function	Phosphatidylinositol-3,4,5-trisphosphate binding	IDA	19203586
GO:0005634	Component	Nucleus	IDA	20333297
GO:0005634	Component	Nucleus	TAS	21432781
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	19203586, 25190803
GO:0005737	Component	Cytoplasm	ISS
GO:0005737	Component	Cytoplasm	TAS	21432781
GO:0005739	Component	Mitochondrion	IEA
GO:0005819	Component	Spindle	IEA
GO:0005829	Component	Cytosol	IDA	21045808
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	14749367, 19203586, 20333297
GO:0005886	Component	Plasma membrane	TAS	21432781
GO:0005911	Component	Cell-cell junction	IEA
GO:0005978	Process	Glycogen biosynthetic process	IEA
GO:0005979	Process	Regulation of glycogen biosynthetic process	IMP	8940145
GO:0006006	Process	Glucose metabolic process	IEA
GO:0006412	Process	Translation	IEA
GO:0006417	Process	Regulation of translation	IEA
GO:0006468	Process	Protein phosphorylation	IDA	11994271, 14749367, 23431171
GO:0006469	Process	Negative regulation of protein kinase activity	IMP	9373175
GO:0006469	Process	Negative regulation of protein kinase activity	ISS
GO:0006606	Process	Protein import into nucleus	IMP	16280327
GO:0006809	Process	Nitric oxide biosynthetic process	TAS	10376602
GO:0006924	Process	Activation-induced cell death of T cells	IMP	14749367
GO:0006954	Process	Inflammatory response	IEA
GO:0006974	Process	Cellular response to DNA damage stimulus	IEA
GO:0006979	Process	Response to oxidative stress	ISS
GO:0007165	Process	Signal transduction	TAS	21432781
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	IDA	20878056
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	10570282
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	IMP	26514923
GO:0007281	Process	Germ cell development	IEA
GO:0007568	Process	Aging	IEA
GO:0008283	Process	Cell population proliferation	TAS	21432781
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	10983986
GO:0008286	Process	Insulin receptor signaling pathway	IMP	8978681
GO:0008637	Process	Apoptotic mitochondrial changes	IEA
GO:0008643	Process	Carbohydrate transport	IEA
GO:0009408	Process	Response to heat	TAS	10958679
GO:0010507	Process	Negative regulation of autophagy	IMP	18387192
GO:0010595	Process	Positive regulation of endothelial cell migration	IMP	18558630
GO:0010628	Process	Positive regulation of gene expression	IMP	28341552
GO:0010628	Process	Positive regulation of gene expression	ISS	18292230
GO:0010629	Process	Negative regulation of gene expression	IEA
GO:0010748	Process	Negative regulation of long-chain fatty acid import across plasma membrane	IMP	16814735
GO:0010761	Process	Fibroblast migration	NAS	19126672
GO:0010763	Process	Positive regulation of fibroblast migration	IEA
GO:0010765	Process	Positive regulation of sodium ion transport	IEA
GO:0010907	Process	Positive regulation of glucose metabolic process	IMP	16814735
GO:0010918	Process	Positive regulation of mitochondrial membrane potential	IMP	10983986
GO:0010951	Process	Negative regulation of endopeptidase activity	IMP	18387192
GO:0010975	Process	Regulation of neuron projection development	ISS
GO:0014065	Process	Phosphatidylinositol 3-kinase signaling	IMP	26514923
GO:0015630	Component	Microtubule cytoskeleton	IDA
GO:0016242	Process	Negative regulation of macroautophagy	NAS	23778976
GO:0016301	Function	Kinase activity	IDA	14749367
GO:0016310	Process	Phosphorylation	IDA	20333297
GO:0016567	Process	Protein ubiquitination	IEA
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	16139227, 32322062
GO:0018105	Process	Peptidyl-serine phosphorylation	TAS	21711983
GO:0018107	Process	Peptidyl-threonine phosphorylation	IDA	20605787
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019899	Function	Enzyme binding	ISS
GO:0021510	Process	Spinal cord development	IEA
GO:0030027	Component	Lamellipodium	NAS	19126672
GO:0030030	Process	Cell projection organization	IEA
GO:0030154	Process	Cell differentiation	TAS	21432781
GO:0030163	Process	Protein catabolic process	IEA
GO:0030212	Process	Hyaluronan metabolic process	IEA
GO:0030235	Function	Nitric-oxide synthase regulator activity	IMP	10376603
GO:0030307	Process	Positive regulation of cell growth	IDA	19203586
GO:0030334	Process	Regulation of cell migration	IMP	19934221
GO:0030334	Process	Regulation of cell migration	TAS	21432781
GO:0031018	Process	Endocrine pancreas development	TAS
GO:0031234	Component	Extrinsic component of cytoplasmic side of plasma membrane	NAS	19126672
GO:0031295	Process	T cell costimulation	TAS
GO:0031397	Process	Negative regulation of protein ubiquitination	IMP	18292230
GO:0031641	Process	Regulation of myelination	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IEA
GO:0031929	Process	TOR signaling	NAS	23778976
GO:0031982	Component	Vesicle	IDA	16792529
GO:0031999	Process	Negative regulation of fatty acid beta-oxidation	IMP	16814735
GO:0032079	Process	Positive regulation of endodeoxyribonuclease activity	IDA	20605787
GO:0032091	Process	Negative regulation of protein binding	IMP	18292230
GO:0032094	Process	Response to food	IEA
GO:0032148	Process	Activation of protein kinase B activity	TAS
GO:0032270	Process	Positive regulation of cellular protein metabolic process	ISS
GO:0032287	Process	Peripheral nervous system myelin maintenance	IEA
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA
GO:0032794	Function	GTPase activating protein binding	IEA
GO:0032869	Process	Cellular response to insulin stimulus	IMP	16814735
GO:0032869	Process	Cellular response to insulin stimulus	ISS
GO:0032991	Component	Protein-containing complex	IDA	10983986, 20878056
GO:0033138	Process	Positive regulation of peptidyl-serine phosphorylation	IDA	19667065
GO:0034405	Process	Response to fluid shear stress	IMP	10376603
GO:0034614	Process	Cellular response to reactive oxygen species	IMP	26514923
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0035556	Process	Intracellular signal transduction	IDA	14749367
GO:0035655	Process	Interleukin-18-mediated signaling pathway	IDA	21321938
GO:0035924	Process	Cellular response to vascular endothelial growth factor stimulus	IEA
GO:0036064	Component	Ciliary basal body	IEA
GO:0038061	Process	NIK/NF-kappaB signaling	IMP	26514923
GO:0042593	Process	Glucose homeostasis	IEA
GO:0042802	Function	Identical protein binding	IPI	7891724, 17554339
GO:0042803	Function	Protein homodimerization activity	IDA	10983986
GO:0042981	Process	Regulation of apoptotic process	ISS
GO:0043065	Process	Positive regulation of apoptotic process	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IDA	19203586
GO:0043066	Process	Negative regulation of apoptotic process	IMP	10983986
GO:0043154	Process	Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	ISS
GO:0043276	Process	Anoikis	NAS	23778976
GO:0043325	Function	Phosphatidylinositol-3,4-bisphosphate binding	IDA	19203586
GO:0043488	Process	Regulation of mRNA stability	TAS
GO:0043491	Process	Protein kinase B signaling	IMP	28341552
GO:0043491	Process	Protein kinase B signaling	TAS
GO:0043536	Process	Positive regulation of blood vessel endothelial cell migration	IDA	20011604
GO:0045429	Process	Positive regulation of nitric oxide biosynthetic process	IMP	10376603
GO:0045600	Process	Positive regulation of fat cell differentiation	IMP	8940145
GO:0045725	Process	Positive regulation of glycogen biosynthetic process	IMP	16814735
GO:0045725	Process	Positive regulation of glycogen biosynthetic process	NAS	17925406
GO:0045737	Process	Positive regulation of cyclin-dependent protein serine/threonine kinase activity	IMP	18483258
GO:0045742	Process	Positive regulation of epidermal growth factor receptor signaling pathway	TAS
GO:0045746	Process	Negative regulation of Notch signaling pathway	TAS
GO:0045792	Process	Negative regulation of cell size	IEA
GO:0045861	Process	Negative regulation of proteolysis	IMP	18387192
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	26514923
GO:0045907	Process	Positive regulation of vasoconstriction	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0046326	Process	Positive regulation of glucose import	IMP	8940145, 16814735
GO:0046329	Process	Negative regulation of JNK cascade	IEA
GO:0046622	Process	Positive regulation of organ growth	IEA
GO:0046777	Process	Protein autophosphorylation	TAS	16280327
GO:0046889	Process	Positive regulation of lipid biosynthetic process	IDA	32322062
GO:0046889	Process	Positive regulation of lipid biosynthetic process	IMP	8940145
GO:0048009	Process	Insulin-like growth factor receptor signaling pathway	IMP	8978681
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IDA	21321938
GO:0050999	Process	Regulation of nitric-oxide synthase activity	TAS
GO:0051000	Process	Positive regulation of nitric-oxide synthase activity	IMP	10376603
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IDA	19057511
GO:0051146	Process	Striated muscle cell differentiation	IEA
GO:0051721	Function	Protein phosphatase 2A binding	IEA
GO:0051898	Process	Negative regulation of protein kinase B signaling	TAS
GO:0060079	Process	Excitatory postsynaptic potential	NAS	21711983
GO:0060416	Process	Response to growth hormone	ISS
GO:0060644	Process	Mammary gland epithelial cell differentiation	TAS	21432781
GO:0060716	Process	Labyrinthine layer blood vessel development	IEA
GO:0070141	Process	Response to UV-A	IDA	18483258
GO:0071260	Process	Cellular response to mechanical stimulus	IEA
GO:0071276	Process	Cellular response to cadmium ion	IMP	26514923
GO:0071356	Process	Cellular response to tumor necrosis factor	IMP	10983986
GO:0071364	Process	Cellular response to epidermal growth factor stimulus	IEA
GO:0071380	Process	Cellular response to prostaglandin E stimulus	IEA
GO:0071407	Process	Cellular response to organic cyclic compound	IEA
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0071889	Function	14-3-3 protein binding	IPI	10102273
GO:0071901	Process	Negative regulation of protein serine/threonine kinase activity	TAS	28386764
GO:0072655	Process	Establishment of protein localization to mitochondrion	IMP	23962723
GO:0072656	Process	Maintenance of protein location in mitochondrion	IMP	23962723
GO:0090201	Process	Negative regulation of release of cytochrome c from mitochondria	ISS
GO:0097011	Process	Cellular response to granulocyte macrophage colony-stimulating factor stimulus	IEA
GO:0097194	Process	Execution phase of apoptosis	IEA
GO:0098794	Component	Postsynapse	IEA
GO:0100002	Process	Negative regulation of protein kinase activity by protein phosphorylation	TAS	21711983
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:0140052	Process	Cellular response to oxidised low-density lipoprotein particle stimulus	IMP	28341552
GO:1900087	Process	Positive regulation of G1/S transition of mitotic cell cycle	IMP	18483258
GO:1900182	Process	Positive regulation of protein localization to nucleus	IMP	20605787
GO:1901215	Process	Negative regulation of neuron death	NAS	18221368
GO:1901796	Process	Regulation of signal transduction by p53 class mediator	TAS
GO:1902176	Process	Negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	NAS	16604263
GO:1903038	Process	Negative regulation of leukocyte cell-cell adhesion	IMP	28341552
GO:1903078	Process	Positive regulation of protein localization to plasma membrane	IMP	8940145
GO:1903721	Process	Positive regulation of I-kappaB phosphorylation	IMP	26514923
GO:1990090	Process	Cellular response to nerve growth factor stimulus	IMP	20605787
GO:1990418	Process	Response to insulin-like growth factor stimulus	ISS
GO:2000010	Process	Positive regulation of protein localization to cell surface	IEA
GO:2000402	Process	Negative regulation of lymphocyte migration	IMP	28341552
GO:2001240	Process	Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	TAS	10748004

Other IDs

• MIM: 164730
• HGNC: 391
• e!Ensembl: ENSG00000142208

Protein

• UniProt ID: P31749
• Protein name: RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha)
• 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 (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). 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 (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). 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 (PubMed:12150915). 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 (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). 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) (PubMed:9829964). 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 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). 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 (By similarity). 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) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF-I (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). 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 (PubMed:20086174, PubMed:20231902). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PubMed:32322062). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865).
• PDB: 1H10, 1UNP, 1UNQ, 1UNR, 2UVM, 2UZR, 2UZS, 3CQU, 3CQW, 3MV5, 3MVH, 3O96, 3OCB, 3OW4, 3QKK, 3QKL, 3QKM, 4EJN, 4EKK, 4EKL, 4GV1, 5KCV, 6BUU, 6CCY, 6HHF, 6HHG, 6HHH, 6HHI, 6HHJ, 6NPZ, 6S9W, 6S9X
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00169	PH	6 → 108	PH domain	Domain
  PF00069	Pkinase	150 → 408	Protein kinase domain	Domain
  PF00433	Pkinase_C	429 → 474	Protein kinase C terminal domain	Family

• Sequence:

  MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQC
  QLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDF
  RSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKI
  LKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLS
  RERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGI
  KDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFEL
  ILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKK
  LSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA
  

• Sequence length: 480