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Domain

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.

Function

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).

Post-translational modifications

Autophosphorylation regulates kinase activity. Phosphorylation on Tyr-518 is required for interaction with SRC and is observed during association with clathrin-coated pits.

Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced by EGF and is lysosome-dependent (By similarity).

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Tissue specificity

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.

Cellular localization

  • Cell membrane
  • Nucleus
  • Endosome
  • Cell junction
  • Adherens junction
  • Cytoplasmic vesicle membrane
  • Peripheral membrane protein
  • Cytoplasmic side
  • Cytoplasmic vesicle
  • Clathrin-coated vesicle
  • Membrane
  • Clathrin-coated pit
  • Cytoplasm
  • Perinuclear region
  • Cytoplasm
  • Cytosol
  • The Tyr-284 phosphorylated form is found both in the membrane and nucleus (By similarity). Co-localizes with EGFR on endosomes (PubMed:20333297). Nuclear translocation is CDC42-dependent (By similarity). Detected in long filamentous cytosolic structures where it co-localizes with CTPS1 (By similarity).

Alternative names

ACK1, TNK2, Activated CDC42 kinase 1, ACK-1, Tyrosine kinase non-receptor protein 2

Target type

Proteins

Primary research area

Oncology

Molecular weight

114569Da

We found 2 products in 2 categories

Primary Antibodies

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Application

Reactive species

Cell Lines & Lysates

Target

Cell type

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