RAC-gamma serine/threonine-protein kinase

UniProt Q9Y243 Organism Homo sapiens Gene AKT3, PKBG EC 2.7.11.1

Also known as: AKT3, PKBG

Function

AKT3 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. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.

Classification

Family (Pfam): PF00169 PH, PF00069 Pkinase, PF00433 Pkinase_C
InterPro: AGC-kinase_C, Akt3, Kinase-like_dom_sf, PH-like_dom_sf, PH_domain, PH_PKB, Pkinase_C, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: Phosphoribosyltransferases & related

Experimental structures · PDB · 2

2X18 X-ray 1.46A
8ZXW X-ray 1.33A

A predicted model is available from AlphaFold.

Gene Ontology · 20

Disease associations

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 MONDO:0014407

Drugs targeting this protein · 12

MK-2206 inhibitor
XL-418 inhibitor
IPATASERTIB inhibitor
AFURESERTIB inhibitor
CAPIVASERTIB inhibitor
UPROSERTIB inhibitor
MIRANSERTIB inhibitor
PIFUSERTIB negative allosteric modulator
TRICIRIBINE PHOSPHATE inhibitor
TAS0612 inhibitor
RUPITASERTIB inhibitor
GSK-690693 inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

RAC-gamma serine/threonine-protein kinase 4 shared papers
RAC-beta serine/threonine-protein kinase 6 shared papers
Phosphatidylinositol 3-kinase regulatory subunit beta 2 shared papers
T-cell leukemia/lymphoma protein 1A 2 shared papers
RAC-alpha serine/threonine-protein kinase 6 shared papers
RAC-beta serine/threonine-protein kinase 2 shared papers
T-cell leukemia/lymphoma protein 1B 1 shared papers
Protein kinase C zeta type 1 shared papers
Protein p13 MTCP-1 1 shared papers
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 1 shared papers
E3 ubiquitin-protein ligase TTC3 1 shared papers
RAC-alpha serine/threonine-protein kinase 1 shared papers

Literature · 31 cited papers

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes: MCAP and MPPH. Clin. Genet. · 2014
De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat. Genet. · 2012
De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat. Genet. · 2012
Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron · 2012
Akt signalling in health and disease. Cell. Signal. · 2011
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-delta in normal human dermal fibroblasts. J. Invest. Dermatol. · 2011
Akt2 and Akt3 play a pivotal role in malignant gliomas. Neuro-oncol. · 2010
The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt. Dev. Cell · 2009
The Akt isoforms are present at distinct subcellular locations. Am. J. Physiol. · 2010
The E3 ligase TRAF6 regulates Akt ubiquitination and activation. Science · 2009
… and 19 more in the literature graph

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