Protein / target
RAC-gamma serine/threonine-protein kinase
Protein at a glance
Biological role
Protein serine/threonine kinase
Strongest disease association
Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
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.
View complete UniProt function annotationHide complete annotation
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
Subcellular location
Domains and Gene Ontology detail (23)Hide
Domains & features
Gene Ontology
- Ccytosol
- Cmembrane
- Cnucleoplasm
- FATP binding
- Fprotein kinase activity
- Fprotein serine kinase activity
- Fprotein serine/threonine kinase activity
- Pinsulin receptor signaling pathway
- Pintracellular signal transduction
- Pnegative regulation of apoptotic process
- Pnegative regulation of cellular senescence
- Pnegative regulation of PERK-mediated unfolded protein response
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Cell proliferation & survival
- ·AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3)…
- ·PIP3 activates AKT signaling
- ·CD28 dependent PI3K/Akt signaling
Cell migration
- ·positive regulation of blood vessel endothelial cell migration
- ·positive regulation of cell migration involved in sprouting angiogenesis
- ·RUNX2 regulates genes involved in cell migration
Receptor tyrosine kinase signalling
- ·Downregulation of ERBB2:ERBB3 signaling
Oncogenic signalling
- ·Constitutive Signaling by AKT1 E17K in Cancer
Cell-cycle regulation
- ·Cyclin E associated events during G1/S transition
Apoptosis & cell death
- ·AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3)…
- ·negative regulation of apoptotic process
View underlying pathways (25)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Broader indication categories (1)Hide
Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.
Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Serine/threonine-protein kinase AKT inhibitor
Serine/threonine-protein kinase AKT inhibitor
Indicated for Breast Neoplasms, Neoplasms
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene AKT3
Gene-level evidence surfaced through the gene AKT3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Drug development
13 compounds recorded · 1 approved · 12 in clinical development
View all recorded compounds (10)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (11)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Indication expanded
Indication expansion: CAPIVASERTIB (NDA218197)
- Label change
Label change: CAPIVASERTIB (NDA218197)
- Label change
Label change: CAPIVASERTIB (NDA218197)
- Label change
Label change: CAPIVASERTIB (NDA218197)
- Label change
Label change: CAPIVASERTIB (NDA218197)
- Regulatory approval
Approval: Truqap (EMA)
- New publicationCapivasertib: A Novel AKT Inhibitor Approved for Hormone-Receptor-Positive, HER-2-Negative Metastatic Breast Cancer.
- New publicationFirst-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.
- Regulatory approval
Approval: CAPIVASERTIB (NDA218197)
- New publicationCapivasertib in Hormone Receptor-Positive Advanced Breast Cancer.
- New publicationCirculating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial.
- New publicationCapivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.