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FLASH GENE

Symbol

AKT2

contributors: mct/npt/pgu - updated : 24-08-2017

HGNC name	v-akt murine thymoma viral oncogene homolog 2
HGNC id	392

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	55.20 kb     14 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001626 14 - 5317 NP_001617 55.8 481 - 1992 1409633 NM_001243028 13 - 5187 NP_001229957 - 419 - - NM_001243027 14 - 5280 NP_001229956 - 419 - -

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive intestine small intestine     highly Lymphoid/Immune spleen       highly   thymus       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a SH2 and a pleckstrin homology (PH) N terminal domains
	a short alpha helical linker
	a C terminal kinase domain

HOMOLOGY

interspecies	homolog to V-akt murine thymoma viral oncogene 2
	homolog to C.elegans F28H6.1

Homologene

FAMILY	protein kinase superfamily
	AGC Ser/Thr protein kinase family
	RAC subfamily

CATEGORY

enzyme , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	mitochondrial localization of AKT2 raises the possibility that this isoform may be involved in both glucose-based energy metabolism and suppression of apoptosis

basic FUNCTION	AKT is a key regulator for cell growth, cell survival
	playing a central role in insulin sensitivity
	enhances palladin expression by maintaining protein stability and upregulating transcription
	AKT2 is indispensable for the regulation of preadipocyte and adipocyte number, whereas AKT1 and AKT2 are equally important for the regulation of insulin-stimulated metabolic pathways in human adipocytes
	protective effects of AKT2 on the aortic wall, that may serve as a therapeutic target in the prevention of Aortic aneurysm and dissection (AAD)
	ASAH1 and AKT2 cooperate to induce malignant transformation
	is essential to maintain podocyte viability and function during chronic kidney disease
	is potentially important for neutrophil recruitment and neutrophil-platelet interactions under thromboinflammatory conditions such as sickle cell disease (SCD)
	specific function for AKT2 in mediating survival of PTEN-deficient tumors
	serine/threonine protein kinase AKT2 is critically involved in insulin-dependent RAC1 activation
	both AKT1 and AKT2 are involved in albumin endocytosis, and phosphorylation of DAB2 by AKT induces albumin endocytosis in proximal tubule epithelial cells
	macrophage AKT2 regulates migration, the inflammatory response and cholesterol metabolism

CELLULAR PROCESS	cell life, proliferation/growth
	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

text	maintenance of normal glucose homeostasis, survival of lymphoid and other cell types

PATHWAY

metabolism

signaling

PI3K/AKT/MTOR signaling pathway is involved in regulation of SPHK1, with AKT2 playing a key role in PDGF-induced SPHK1 expression in coronary artery smooth muscle cells

a component

INTERACTION

DNA

RNA

small molecule

protein	phosphorylating and inactivating components of the apoptotic machinery including BAD, CASP9 and the transcription factor FKHRL1 (phosphatidyl inositol)
	down regulating hyperproliferation and antiapoptotic activities induced by IGF1R hyperstimulation
	preferential interaction between WDFY2 and AKT2 that promotes the maintenance of AKT2 protein levels
	MAPKAP1/CRTC2-AKT2 signaling axis is a key regulator of FOXO1 transcriptional activity in B cells
	SNAI1 enhances the binding of AKT2 to the E-cadherin (CDH1) promoter and AKT2 interference prevents SNAI1 repression of CDH1 gene
	is a negative regulator of NFATC1 activation through its ability to inhibit calcium mobilization from the ER
	regulates RAC1 activity in the insulin-dependent signaling pathway leading to SLC2A4 translocation to the plasma membrane in skeletal muscle cells
	PIK3CA activates AKT1, independently of PDPK1, and AKT2 by cooperating with PDPK1 in the insulin signal transduction pathway linked to SLC2A4 translocation
	binding of CDKN1A to AKT2 in the nucleus is an essential component in determining the specific role of AKT2 in the cell cycle arrest that precedes myogenic differentiation
	enhanced AKT2 or AKT3 activation also promotes reprogramming and coordinates with LIF to activate STAT3
	both AKT1 and AKT2 are involved in albumin endocytosis, and phosphorylation of DAB2 by AKT induces albumin endocytosis in proximal tubule
	APPL1 binds to AKT2, a key molecule in the insulin signaling pathway, thereby enhancing insulin-induced AKT2 activation and downstream signaling leading to insulin action and secretion
	TMOD3 is a novel AKT2 effector regulating insulin-stimulated SLC2A4 exocytosis through cortical actin remodeling
	C terminus of AKT1, AKT2 and the N terminus of VRK2 facilitate the interaction of Akt and VRK2 in mammalian cells

cell & other

REGULATION

activated by	growth factors via PI3K binding to PH domain, induced by insulin growth factor 1, and maybe others activated by phosphatidylinositol 3- kinase in the antiapoptotic PI3K pathway
	coactivated by TCL1

Phosphorylated by

PDK1 that phosphorylates AKT1 at Thr308 and AKT2 at Thr309

Other

CSNK2A1-dependent phosphorylation is a crucial event which, discriminating between AKT1 and AKT2, can account for different substrate specificities

ASSOCIATED DISORDERS

corresponding disease(s)

NIDDM6

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in ovarian carcinoma tumoral   amplification     in ovarian and pancreatic carcinomas tumoral somatic mutation       in the kinase domain occuring in a small fraction of common cancers tumoral       gain of function associated with the survival of melanoma cells tumoral   amplification     amplification of AKT1 and/or AKT2 and high-level polysomy were found in lung carcinomas tumoral fusion       recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer brain glioma/neuroblstoma targeting AKT2 and AKT3 may hold promise for the treatment of patients with gliomas cardiovascular atheroma cardiac argeting AKT2 in macrophages might be beneficial for treating atherosclerosis.

ANIMAL & CELL MODELS

Akt2-deficient mice showed abnormal elastic fibers and reduced medial thickness in the aortic wall