InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PTK2

Summary

InnateDB Protein

IDBP-480322.4

Last Modified

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

Gene Symbol

PTK2

Protein Name

PTK2 protein tyrosine kinase 2

Synonyms

FADK; FAK; FAK1; FRNK; p125FAK; pp125FAK; PPP1R71;

Species

Homo sapiens

Ensembl Protein

ENSP00000429911

InnateDB Gene

IDBG-37147 (PTK2)

Protein Structure

UniProt Annotation

Function

Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269PubMed:10655584, ECO:0000269PubMed:11331870, ECO:0000269PubMed:11980671, ECO:0000269PubMed:15166238, ECO:0000269PubMed:15561106, ECO:0000269PubMed:15895076, ECO:0000269PubMed:16919435, ECO:0000269PubMed:16927379, ECO:0000269PubMed:17395594, ECO:0000269PubMed:17431114, ECO:0000269PubMed:17968709, ECO:0000269PubMed:18006843, ECO:0000269PubMed:18206965, ECO:0000269PubMed:18256281, ECO:0000269PubMed:18292575, ECO:0000269PubMed:18497331, ECO:0000269PubMed:18677107, ECO:0000269PubMed:19138410, ECO:0000269PubMed:19147981, ECO:0000269PubMed:19224453, ECO:0000269PubMed:20332118, ECO:0000269PubMed:20495381, ECO:0000269PubMed:21454698}.

Subcellular Localization

Cell junction, focal adhesion. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cell cortex. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Nucleus. Note=Constituent of focal adhesions. Detected at microtubules.

Disease Associations

Note=Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.

Tissue Specificity

Detected in B and T-lymphocytes. Isoform 1 and isoform 6 are detected in lung fibroblasts (at protein level). Ubiquitous. {ECO:0000269PubMed:20109444, ECO:0000269PubMed:7692878, ECO:0000269PubMed:8247543, ECO:0000269PubMed:8422239}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 166 experimentally validated interaction(s) in this database.
They are also associated with 26 interaction(s) predicted by orthology.

Experimentally validated
Total	166 [view]
Protein-Protein	165 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	26 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008432	JUN kinase binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0042169	SH2 domain binding

Biological Process

GO:0001525	angiogenesis
GO:0001890	placenta development
GO:0001934	positive regulation of protein phosphorylation
GO:0003007	heart morphogenesis
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006921	cellular component disassembly involved in execution phase of apoptosis
GO:0007165	signal transduction
GO:0007172	signal complex assembly
GO:0007229	integrin-mediated signaling pathway
GO:0007411	axon guidance
GO:0007596	blood coagulation
GO:0008284	positive regulation of cell proliferation
GO:0008360	regulation of cell shape
GO:0009790	embryo development
GO:0010594	regulation of endothelial cell migration
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0022408	negative regulation of cell-cell adhesion
GO:0030010	establishment of cell polarity
GO:0030168	platelet activation
GO:0030335	positive regulation of cell migration
GO:0032319	regulation of Rho GTPase activity
GO:0033628	regulation of cell adhesion mediated by integrin
GO:0038007	netrin-activated signaling pathway
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0042127	regulation of cell proliferation
GO:0043066	negative regulation of apoptotic process
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0045667	regulation of osteoblast differentiation
GO:0045860	positive regulation of protein kinase activity
GO:0046777	protein autophosphorylation
GO:0048013	ephrin receptor signaling pathway
GO:0048870	cell motility
GO:0051493	regulation of cytoskeleton organization
GO:0051893	regulation of focal adhesion assembly
GO:0051897	positive regulation of protein kinase B signaling
GO:0060396	growth hormone receptor signaling pathway
GO:2000060	positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000811	negative regulation of anoikis

Cellular Component

GO:0005634	nucleus
GO:0005815	microtubule organizing center
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005925	focal adhesion
GO:0005938	cell cortex

Protein Structure and Domains

PDB ID

InterPro

IPR000299 FERM domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR005189 Focal adhesion kinase, targeting (FAT) domain
IPR011009 Protein kinase-like domain
IPR019748 FERM central domain
IPR019749 Band 4.1 domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR029071 Ubiquitin-related domain

PFAM

PF00069
PF07714
PF03623
PF00373

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00295
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt