Candidate Genes Diabetic Retinopathy

AKT3 v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma)

Official Symbol
AKT3
Alternative Names
RAC-gamma serine/threonine-protein kinase
PKB gamma
OTTHUMP00000037911
OTTHUMP00000037912
RAC-gamma serine/threonine protein kinase
DKFZp434N0250, PKB-GAMMA, PKBG, PRKBG, RAC-PK-gamma, RAC-gamma, STK-2
Description
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. It 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). AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1).
Location
1q44
Map
Chr 17
Start: 243,651,535 bp from pter
End: 244,013,430 bp from pter
Size: 361,896 bases
Orientation: minus strand
Exons and Introns
14 exons and 35 distinct gt-ag introns.
Nucleotide Sequence
Aminoacid Sequence
Variation
rs16356 -/ATT
Motif
Pfam: Pkinase Pkinase_Tyr PH Pkinase_C APH
PROSITE: PROTEIN_KINASE_ST PROTEIN_KINASE_ATP PH_DOMAIN PROTEIN_KINASE_DOM AGC_KINASE_CTER
Ec No.
2.7.11.1
Catalytic Activity
ATP + a protein = ADP + a phosphoprotein
Enzyme Regulation
Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation
Pathway
ErbB signaling pathway
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mTOR signaling pathway
Jak-STAT signaling pathway
Apoptosis
Interactors
Protein interactors
Tuberin
3 Phosphoinositide dependent protein kinase 1
Protein kinase C, zeta
Protein kinase C delta
TCL1 protein
Post Translational Modification
Acetylation
Phosphorylation
Phosphorylation on Thr-305 and Ser-472 is required for full activity Phosphorylated upon DNA damage, probably by ATM or ATR. Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome
Molecular Weight
55774 da
Molecular Class
Serine/threonine kinase
Molecular Function
Transferase IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival. Capable of phosphorylating several known proteins. Truncated isoform 2/PKB gamma 1 without the second serine phosphorylation site could still be stimulated but to a lesser extent
3D Structure