Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TNK2 (Q07912) - Overview - Molecular Target Synopsis

Protein


TNK2, Activated CDC42 kinase 1
Enzyme Classification 2.7.10.2
UniProt Q07912

Also Known as ACK1_HUMAN, TNK2, ACK1

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). 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.

5ZXB
CRYSTAL STRUCTURE OF ACK1 WITH COMPOUND 10D
RCSB/PDB
Inspect Structure
See all 3D Structures for TNK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: TNK2 is active in the following subcellular-locations: adherens junction, cell junction, cell membrane, clathrin-coated pit, clathrin-coated vesicle, cytoplasm, cytoplasmic vesicle, cytoplasmic vesicle membrane, endosome, membrane, nucleus, perinuclear region.
GO terms: TNK2 is active in the following subcellular-locations: adherens junction, clathrin-coated pit, clathrin-coated vesicle, cytoophidium, cytoplasm, cytoplasmic vesicle membrane, endosome, Grb2-EGFR complex, membrane, nucleus, perinuclear region of cytoplasm, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TNK2 has gain in 6 cell-lines, loss in 1 cell-lines and no signal in 998 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: COLO205, MCF7, T47D

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: COLO 206F, COLO 205, MDA-MB-134-VI

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

RNA Interference


TNK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM149, HCC70. (see details)

3D Structures


For TNK2 there are:
11 structures (22 chains) solved
7 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TNK2 has been screened with 1167 compounds (1918 bioactivities), 236 compounds have bioactivities that show binding affinity of <= 500nM (322 bioactivities). (see details)