ETNK2

Activated CDC42 kinase 1 UniProt accession Q07912

Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX.

Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1.

May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs).

Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels.

Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370)

Source: UniProt

Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4 (By similarity). Homodimer.

Interacts with AR, CDC42, WWASL and WWOX. Interacts with CSPG4 (activated). Interacts with MERTK (activated); stimulates autophosphorylation.

May interact (phosphorylated) with HSP90AB1; maintains kinase activity. Interacts with NPHP1. Interacts with SNX9 (via SH3 domain).

Interacts with SRC (via SH2 and SH3 domain). Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts (via kinase domain) with AKT1.

Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms complexes with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by TNK2

Source: UniProt
Cell membrane, Nucleus, Endosome, Cell junction, adherens junction, Cytoplasmic vesicle membrane — Peripheral membrane protein, Cytoplasmic vesicle, clathrin-coated vesicle, Membrane, clathrin-coated pit, Cytoplasm, perinuclear region, Cytoplasm, cytosol
Source: UniProt

The Tyr-284 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages. It also shows a significant increase in expression in prostate cancers during the progressive stages

Source: UniProt

The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR

The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and dimerization to allow for autophosphorylation

The UBA domain binds both poly- and mono-ubiquitin

Source: UniProt
  • Signaling by LTK
Source: Reactome via UniProt

Mutations

No mutation information available.

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to ETNK2, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 2

NCT ID Condition Brief Title Phase Status
NCT06705686 Metastatic Castration-resistant Prostate Cancer (CRPC), Metastatic Castration-resistant Prostate Carcinoma Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer PHASE1 RECRUITING
NCT07375966 Ischemic Stroke Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Tenecteplase (RITIS-TNK2) PHASE2 RECRUITING