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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

AKT1 Gene

protein-coding GIFtS: 79
GCID: GC14M105235

v-akt murine thymoma viral oncogene homolog 1

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AKT1 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
V-Akt Murine Thymoma Viral Oncogene Homolog 1¹ ²		PKB Alpha² ³
PKB¹ ² ³		EC 2.7.11.1³ ⁸
RAC¹ ² ³		PKB-ALPHA²
AKT¹ ²		RAC-ALPHA²
PRKBA¹ ²		Rac Protein Kinase Alpha²
Protein Kinase B Alpha² ³		RAC-Alpha Serine/Threonine-Protein Kinase²
Proto-Oncogene C-Akt² ³		Protein Kinase B³
RAC-PK-Alpha¹		EC 2.7.11⁸

External Ids:	HGNC: 391¹	Entrez Gene: 207²	Ensembl: ENSG00000142208⁷	OMIM: 164730⁵	UniProtKB: P31749³

Export aliases for AKT1 gene to outside databases

Previous GC identifers: GC14M102614 GC14M099226 GC14M103207 GC14M104361 GC14M085432

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for AKT1:

The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and

immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is

rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the

activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator

of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent

manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the

apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively

spliced transcript variants have been found for this gene. (provided by RefSeq, Jul 2011)

UniProtKB/Swiss-Prot: AKT1_HUMAN, P31749

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

Function: 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

summary for AKT1:

Akt (Protein kinase B, PKB) is a serine/threonine kinase that plays a key in regulating cell survival,

insulin signaling, angiogenesis and tumor formation. Akt is a downstream mediator of the PI 3-K pathway,

resulting in the recruitment of Akt to the plasma membrane via the PH (plexstrin homology domain) of Akt.

Akt is fully activated by phosphorylation at two key sites: Ser308 (phosphorylated by PDK1) and Thr478

(phosphorylated by mTOR and DNA-PK). Akt can then phosphorylated a wide range of substrates including

transcription factors (e.g. FOXO1), kinases (GSK-3, Raf-1, ASK, Chk1) and other proteins with important

signaling roles (e.g. Bad, MDM2). There are three isoforms of Akt; Akt 1, 2 and 3 (also known as PKBalpha,

beta and gamma).

Gene Wiki entry for AKT1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000014.8 NC_018925.1 NT_026437.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the AKT1 gene promoter:
CREB deltaCREB
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): AKT1 promoter sequence

Search SABiosciences Chromatin IP Primers for AKT1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat AKT1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 14q32.32 Ensembl cytogenetic band: 14q32.33 HGNC cytogenetic band: 14q32.32-q32.33

AKT1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
AKT1 gene location

GeneLoc information about chromosome 14 GeneLoc Exon Structure

GeneLoc location for GC14M105235: view genomic region (about GC identifiers)

Start:	105,235,686 bp from pter	End:	105,262,088 bp from pter
Size:	26,403 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: AKT1_HUMAN, P31749 (See protein sequence)

Recommended Name: RAC-alpha serine/threonine-protein kinase

Size: 480 amino acids; 55686 Da

Subunit: Interacts (via the C-terminus) with CCDC88A (via its C-terminus). Interacts with GRB10; the interaction leads

to GRB10 phosphorylation thus promoting YWHAE-binding (By similarity). Interacts with AGAP2 (isoform 2/PIKE-A); the

interaction occurs in the presence of guanine nucleotides. Interacts with AKTIP. Interacts (via PH domain) with MTCP1,

TCL1A AND TCL1B. Interacts with CDKN1B; the interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle

progression. Interacts with MAP3K5 and TRAF6. Interacts with BAD, PPP2R5B, STK3 and STK4. Interacts (via PH domain)

with SIRT1. Interacts with SRPK2 in a phosphorylation-dependent manner. Interacts with RAF1. Interacts with TRIM13;

the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with TNK2 and CLK2. Interacts

(via the C-terminus) with THEM4 (via its C-terminus). Interacts with and phosphorylated by PDPK1

Subcellular location: 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 where it is targeted for further phosphorylations on Thr-308 and

Ser-473 leading to its activation and the activated form translocates to the nucleus

Caution: In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play

redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase

isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more

specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific

for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of

cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though

it appears to be predominantly expressed in brain

6/20 PDB 3D structures from and Proteopedia for AKT1 (see all 20):

1H10 (3D)

1UNP (3D)

1UNQ (3D)

1UNR (3D)

2UVM (3D)

2UZR (3D)

Secondary accessions: B2RAM5 Q9BWB6

Explore the universe of human proteins at neXtProt for AKT1: NX_P31749

Post-translational modifications:

O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating phosphorylation at Thr-308 via disrupting the interaction

between AKT1 and PDPK1. O-GlcNAcylation at Ser-473 also probably interferes with phosphorylation at this site¹

Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity. Activated TNK2 phosphorylates it on

Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA. This phosphorylated form localizes to

the cell membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading

to its activation. Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation by PDPK1. Ser-473 phosphorylation

is enhanced by interaction with AGAP2 isoform 2 (PIKE-A). Ser-473 phosphorylation is enhanced in focal cortical

dysplasias with Taylor-type balloon cells. Ser-473 phosphorylation is enhanced by signaling through activated FLT3.

Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase. The phosphorylated form of PPP2R5B is required for

bridging AKT1 with PP2A phosphatase¹

Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome (By

similarity). Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced

'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation. When ubiquitinated, it

translocates to the plasma membrane, where it becomes phosphorylated. When fully phosphorylated and translocated into

the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.

Also ubiquitinated by TRIM13 leading to its proteasomal degradation¹

Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases EP300 and KAT2B. Acetylation results in reduced

phosphorylation and inhibition of activity. Deacetylated at Lys-14 and Lys-20 by SIRT1. SIRT1-mediated deacetylation

relieves the inhibition¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P31749

4/35 DME Specific Peptides for AKT1 (P31749) (see all 35)

VVYRDLK

YYAMKIL

GVVMYEM

AEIVSAL

AKT1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_001014431.1 NP_001014432.1 NP_005154.2

ENSEMBL proteins:

ENSP00000451828 ENSP00000384293 ENSP00000270202 ENSP00000385326 ENSP00000450688

ENSP00000451470 ENSP00000450681 ENSP00000443897 ENSP00000451166 ENSP00000451290

ENSP00000451824

Reactome Protein details: P31749
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant AKT1 Protein
	R&D Systems Recombinant & Natural Proteins for AKT1
	Enzo Life Sciences proteins for AKT1
	OriGene Purified Proteins (see all 3): AKT1 OriGene Protein Over-expression Lysate (see all 4): AKT1 OriGene Custom Protein Services for AKT1
	GenScript Custom Purified and Recombinant Proteins Services for AKT1
	Novus Biologicals AKT1 Proteins Novus Biologicals AKT1 Lysates
	Sino Biological Recombinant Protein for AKT1
	ProSpec Recombinant Protein for AKT1
	Browse Proteins at Uscn

Gene Ontology (GO): 5/9 cellular component terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005625	soluble fraction	--	--
GO:0005634	nucleus	TAS	--
GO:0005654	nucleoplasm	TAS	--
GO:0005737	cytoplasm	TAS	--
GO:0005819	spindle	IEA	--

AKT1 for ontologies About GeneDecksing

AKT1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of AKT1
	R&D Systems Antibodies for AKT1
	Cell Signaling Technology (CST) Antibodies for AKT1
	OriGene Antibodies (see all 20): AKT1 OriGene Custom Antibody Services for AKT1
	GenScript Superior Antibodies for AKT1
	Novus Biologicals AKT1 Antibodies
	Abcam antibodies for AKT1
	Browse Antibodies at Uscn
	ThermoFisher Antibody for AKT1

Assay Products for AKT1:

	EMD Millipore Kits and Assays for the Analysis of AKT1
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for AKT1 (see all)
	GenScript AKT1-Activity-based Kinase Assay for Compound Screening
	Cell Signaling Technology (CST) Sandwich ELISA Kits for AKT1
	Enzo Life Sciences assays for AKT1
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

AKT1 for domains About GeneDecksing

5/9 InterPro domains/families (see all 9):

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR000961 AGC-kinase_C

IPR011009 Kinase-like_dom

IPR017892 Pkinase_C

Graphical View of Domain Structure for InterPro Entry P31749

ProtoNet protein and cluster: P31749

2 Blocks protein families:

IPB000961 Protein kinase C-terminal domain

IPB001849 Pleckstrin-like

UniProtKB/Swiss-Prot: AKT1_HUMAN, P31749

Domain: Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following

phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. The PH domain

mediates interaction with TNK2 and Tyr-176 is also essential for this interaction

Domain: The AGC-kinase C-terminal mediates interaction with THEM4

Similarity: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily

Similarity: Contains 1 AGC-kinase C-terminal domain

Similarity: Contains 1 PH domain

Similarity: Contains 1 protein kinase domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: