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

PTK2 (Q05397) - Overview - Molecular Target Synopsis

Protein


PTK2, Focal adhesion kinase 1
Enzyme Classification 2.7.10.2
UniProt Q05397

Also Known as FAK1_HUMAN, PTK2, FAK, FAK1

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. Interacts (via first Pro-rich region) with CAS family members (via SH3 domain), including BCAR1, BCAR3, CASS4 and NEDD9. Interacts with GIT1. Interacts with SORBS1. Interacts with ARHGEF28. Interacts with SHB. Interacts with PXN and TLN1. Interacts with STAT1. Interacts with DCC. Interacts with WASL. Interacts with ARHGEF7. Interacts with GRB2 and GRB7 (By similarity). Component of a complex that contains at least FER, CTTN and PTK2/FAK1. Interacts with BMX. Interacts with TGFB1I1. Interacts with STEAP4. Interacts with ZFYVE21. Interacts with ESR1. Interacts with PIK3R1 or PIK3R2. Interacts with SRC, FGR, FLT4 and RET. Interacts with EPHA2 in resting cells; activation of EPHA2 recruits PTPN11, leading to dephosphorylation of PTK2/FAK1 and dissociation of the complex. Interacts with EPHA1 (kinase activity-dependent). Interacts with CD4; this interaction requires the presence of HIV-1 gp120. Interacts with PIAS1. Interacts with ARHGAP26 and SHC1. Interacts with RB1CC1; this inhibits PTK2/FAK1 activity and activation of downstream signaling pathways. Interacts with P53/TP53 and MDM2. Interacts with LPXN (via LD motif 3). Interacts with MISP. Interacts with CIB1 isoform 2. Interacts with CD36. Interacts with EMP2; regulates PTK2 activation and localization (PubMed:19494199).

6I8Z
CRYSTAL STRUCTURE OF PTK2 IN COMPLEX WITH BI-4464.
RCSB/PDB
Inspect Structure
See all 3D Structures for PTK2

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1065ENSG00000169398ENST00000340930ENSP00000341189Q05397-5
1065ENSG00000169398ENST00000395218ENSP00000378644
1052ENSG00000169398ENST00000521059, ENST00000522684ENSP00000429474, ENSP00000429911Q05397-1
1006ENSG00000169398ENST00000535192ENSP00000438009Q05397-7
965ENSG00000169398ENST00000519654ENSP00000429929
879Q05397-2
753ENSG00000169398ENST00000521986ENSP00000430603
724ENSG00000169398ENST00000523539ENSP00000428492
720ENSG00000169398ENST00000538769ENSP00000445742
680ENSG00000169398ENST00000519465ENSP00000429170
554Q05397-3
431Q05397-4
362ENSG00000169398ENST00000430260ENSP00000403416
360Q05397-6
306ENSG00000169398ENST00000524202ENSP00000429023
175ENSG00000169398ENST00000519024ENSP00000428232
163ENSG00000169398ENST00000520475ENSP00000428792
133ENSG00000169398ENST00000522424ENSP00000427774
132ENSG00000169398ENST00000521562ENSP00000431106
128ENSG00000169398ENST00000521981ENSP00000428593
128ENSG00000169398ENST00000524357ENSP00000429001
127ENSG00000169398ENST00000523803ENSP00000429530
124ENSG00000169398ENST00000517453ENSP00000430951
124ENSG00000169398ENST00000520151ENSP00000428482
120ENSG00000169398ENST00000523435ENSP00000430828
119ENSG00000169398ENST00000521907ENSP00000427795
117ENSG00000169398ENST00000520045ENSP00000430044
115ENSG00000169398ENST00000517712ENSP00000430916
107ENSG00000169398ENST00000521395ENSP00000429907
79ENSG00000169398ENST00000521029ENSP00000429958
73ENSG00000169398ENST00000523388ENSP00000429702
72ENSG00000169398ENST00000521250ENSP00000427972
72ENSG00000169398ENST00000523670ENSP00000428380
67ENSG00000169398ENST00000522950ENSP00000429437
65ENSG00000169398ENST00000521332ENSP00000429409
59ENSG00000169398ENST00000520828ENSP00000427762
57ENSG00000169398ENST00000524040ENSP00000430037
21ENSG00000169398ENST00000523679ENSP00000429028
8ENSG00000169398ENST00000524257ENSP00000431023

Sub-cellular localization


UniProt: PTK2 is active in the following subcellular-locations: cell cortex, cell junction, cell membrane, centrosome, cytoplasm, cytoskeleton, focal adhesion, microtubule organizing center, nucleus.
GO terms: PTK2 is active in the following subcellular-locations: apical plasma membrane, cell cortex, cytoplasm, cytoskeleton, cytosol, dendritic spine, focal adhesion, lamellipodium, microtubule organizing center, nucleus, plasma membrane, stress fiber.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PTK2 has gain in 18 cell-lines, loss in 3 cell-lines and no signal in 983 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HT29, NCI_ADR_RES, OVCAR_8

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H1781, OVCAR-8, NCI-H209

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


PTK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB134VI, SUM44. (see details)

3D Structures


For PTK2 there are:
27 structures (50 chains) solved
19 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PTK2 has been screened with 1819 compounds (2421 bioactivities), 536 compounds have bioactivities that show binding affinity of <= 500nM (669 bioactivities). (see details)