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Ack
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. Belongs to the protein kinase superfamily. Tyr protein kinase family. 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. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
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| Protein type: Ack family; EC 2.7.10.2; EC 2.7.11.1; Kinase, protein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); TK group |
| Chromosomal Location of mouse Ortholog: 16|16 B3 |
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Cellular Component:
anchoring junction; axon; clathrin-coated pit; clathrin-coated vesicle; cytoophidium; cytoplasm; cytoplasmic vesicle; dendrite; endosome; Grb2-EGFR complex; growth cone; intracellular membrane-bounded organelle; membrane; neuronal cell body; nucleus; plasma membrane
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Molecular Function:
ATP binding; epidermal growth factor receptor binding; identical protein binding; kinase activity; metal ion binding; non-membrane spanning protein tyrosine kinase activity; nucleotide binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; protein serine/threonine/tyrosine kinase activity; protein tyrosine kinase activity; transferase activity; ubiquitin protein ligase binding; WW domain binding
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Biological Process:
endocytosis; phosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; protein phosphorylation; regulation of clathrin-dependent endocytosis; signal transduction; spermatid development
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Reference #:
O54967
(UniProtKB)
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Alt. Names/Synonyms: Ack; ACK-1; Ack1; Activated CDC42 kinase 1; activated p21cdc42Hs kinase; AW552477; Cdc42 GTPase-inhibiting protein; Cdgip; MGC37479; Non-receptor protein tyrosine kinase Ack; OTTMUSP00000030887; P21cdc42Hs kinase; Pyk; Pyk1; Tnk2; Tyrosine kinase non-receptor protein 2; tyrosine kinase, non-receptor, 2
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Gene Symbols: Tnk2
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Molecular weight:
116,975 Da
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Basal Isoelectric point:
7.13
Predict pI for various phosphorylation states
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CST Pathways:
Tyrosine Kinases & Substrates
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