InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TNK2

Summary

InnateDB Protein

IDBP-70930.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TNK2

Protein Name

tyrosine kinase, non-receptor, 2

Synonyms

ACK; ACK-1; ACK1; p21cdc42Hs;

Species

Homo sapiens

Ensembl Protein

ENSP00000371341

InnateDB Gene

IDBG-70926 (TNK2)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10652228, ECO:0000269PubMed:11278436, ECO:0000269PubMed:16247015, ECO:0000269PubMed:16257963, ECO:0000269PubMed:16472662, ECO:0000269PubMed:17038317, ECO:0000269PubMed:18262180, ECO:0000269PubMed:18435854, ECO:0000269PubMed:19815557, ECO:0000269PubMed:20333297, ECO:0000269PubMed:20383201}.

Subcellular Localization

Cell membrane. Nucleus. Endosome. Cell junction, adherens junction {ECO:0000250}. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic vesicle, clathrin-coated vesicle. Membrane, clathrin- coated pit. Note=The Tyr-284 phosphorylated form is found both in the membrane and nucleus. Colocalizes with EGFR on endosomes. Nuclear translocation is CDC42-dependent.

Disease Associations

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. {ECO:0000269PubMed:16247015, ECO:0000269PubMed:20333297, ECO:0000269PubMed:20623637}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 88 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	88 [view]
Protein-Protein	88 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005095	GTPase inhibitor activity
GO:0005154	epidermal growth factor receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0046872	metal ion binding
GO:0050699	WW domain binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006897	endocytosis
GO:0007166	cell surface receptor signaling pathway
GO:0007264	small GTPase mediated signal transduction
GO:0016310	phosphorylation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0043086	negative regulation of catalytic activity
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:2000369	regulation of clathrin-mediated endocytosis

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005768	endosome
GO:0005886	plasma membrane
GO:0005905	coated pit
GO:0005912	adherens junction
GO:0016020	membrane
GO:0030136	clathrin-coated vesicle
GO:0030424	axon
GO:0030425	dendrite
GO:0030426	growth cone
GO:0030659	cytoplasmic vesicle membrane
GO:0043025	neuronal cell body
GO:0070436	Grb2-EGFR complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR009060 UBA-like
IPR011009 Protein kinase-like domain
IPR013761 Sterile alpha motif/pointed domain
IPR015116 Cdc42 binding domain like
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR021619 EGFR receptor inhibitor Mig-6

PFAM

PF00069
PF07714
PF00018
PF14604
PF09027
PF11555

PRINTS

PR00109
PR00452

PIRSF

SMART

SM00326
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt