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  7. Focal adhesion kinase 1

Tchem Focal adhesion kinase 1

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.

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene, but the full-length natures of only four of them have been determined. [provided by RefSeq, Oct 2015]

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Property Summary

NCBI Gene PubMed Count 668
PubMed Score 956.94
PubTator Score 1563.61

Knowledge Summary

Patent (30,498)

TINX Plot

  Disease Sources (4)

Disease Target Count P-value
non-small cell lung cancer 2798 5.20375416427961E-16
osteosarcoma 7933 3.04219054959473E-6
ovarian cancer 8492 3.74355328681487E-6
Pick disease 1893 1.11935752130555E-5
Breast cancer 3099 1.99852899189363E-5
intraductal papillary-mucinous adenoma (IPMA) 2956 3.99302393471023E-4
intraductal papillary-mucinous carcinoma (IPMC) 2988 7.58457425943122E-4
pancreatic ductal adenocarcinoma liver metastasis 1795 0.00104294463047861
oligodendroglioma 2849 0.00116324233027692
intraductal papillary-mucinous neoplasm (IPMN) 3289 0.00386451333023526
subependymal giant cell astrocytoma 2287 0.00452263473485876
mucosa-associated lymphoid tissue lymphoma 480 0.00548443525379947
spina bifida 1064 0.0390594781109477
Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Cancer 2346 5.617 2.8

Expression

Synonym

Accession Q05397 B4E2N6 F5H4S4 J3QT16 Q14291 Q8IYN9 Q9UD85 FADK 1
Symbols FAK
FADK
FAK1
FRNK
PPP1R71
p125FAK
pp125FAK

Gene

PTK2

PANTHER Protein Class (4)

PDB

1OW6   1OW7   1OW8   3B71   1K04   1K05   1MP8   2ETM   2IJM   3BZ3   3PXK   3S9O   4EBV   4EBW   4GU6   4GU9   4I4E   4I4F   4K8A   4K9Y   4KAB   4KAO   4NY0   4Q9S  

  Ortholog (9)

Species Source
Chimp OMA EggNOG
Mouse OMA EggNOG Inparanoid
Rat OMA EggNOG Inparanoid
Dog OMA EggNOG Inparanoid
Cow OMA EggNOG Inparanoid
Opossum OMA EggNOG Inparanoid
Platypus OMA EggNOG Inparanoid
Anole lizard OMA Inparanoid
Xenopus OMA Inparanoid

  TechDev Info (1)

Gary Johnson Kinome profile via MIB/MS Technology

 GO Function (11)

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 GO Component (12)

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 GO Process (54)

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 Compartment GO Term (81)

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 MGI Term (18)

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 HCA RNA Cell Line (56)

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Pathway (175)

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 UniProt Keyword (24)

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Ligand (304)  

Structure of CHEMBL207084

CHEMBL207084
pIC50 7.54

Structure of CHEMBL3657336

CHEMBL3657336
pIC50 7.54

Structure of CHEMBL3657327

CHEMBL3657327
pIC50 7.54

Structure of CHEMBL3657375

CHEMBL3657375
pIC50 7.55

Structure of CHEMBL3665937

CHEMBL3665937
pIC50 7.57

Structure of CHEMBL3657314

CHEMBL3657314
pIC50 7.59

Structure of CHEMBL3657301

CHEMBL3657301
pIC50 7.59

Structure of CHEMBL3665876

CHEMBL3665876
pIC50 7.60

Structure of CHEMBL1934343

CHEMBL1934343
pIC50 7.60

Structure of CHEMBL3692186

CHEMBL3692186
pIC50 7.60

Structure of CHEMBL2315584

CHEMBL2315584
pKd 7.62

Structure of CHEMBL2315583

CHEMBL2315583
pKd 7.62

Structure of CHEMBL3692203

CHEMBL3692203
pIC50 7.64

Structure of CHEMBL3692204

CHEMBL3692204
pIC50 7.64

Structure of CHEMBL3642416

CHEMBL3642416
pIC50 7.66

Structure of CHEMBL3692180

CHEMBL3692180
pIC50 7.68

Structure of CHEMBL1934334

CHEMBL1934334
pIC50 7.68

Structure of CHEMBL1934339

CHEMBL1934339
pIC50 7.68

Structure of CHEMBL3665907

CHEMBL3665907
pIC50 7.70

Structure of CHEMBL3692191

CHEMBL3692191
pIC50 7.70

MLP Assay (5)

AID Type Active / Inconclusive / Inactive Description
727 screening 811 / 0 / 96078 Primary biochemical high-throughput screening assay for inhibitors of Focal Adhesion Kinase (FAK)
794 other 212 / 0 / 541 Confirmation biochemical assay for inhibitors of Focal Adhesion Kinase (FAK)
810 confirmatory 110 / 0 / 100 Dose-response biochemical assay for inhibitors of Focal Adhesion Kinase (FAK)
1802 summary 0 / 0 / 0 Summary of probe development efforts to identify inhibitors of Focal Adhesion Kinase (FAK)
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448

Gene RIF (519)

PMID Text
27009091 CEP-37440 decreased the cell proliferation of FC-IBC02, SUM190, and KPL4 by blocking the autophosphorylation kinase activity of FAK1 (Tyr 397).
26992741 Our findings suggest that the targets of FAK play a key role in metastasis
26975850 Increased focal adhesion kinase(FAK)activity.
26962872 Combining erlotinib with FAK inhibitor was also potent in vivo as evidenced by reduced tumor growth in the A549 mouse xenograft model.
26956728 Bit1 may be an important regulator in cell growth, apoptosis, migration and invasion of esophageal squamous cell carcinoma via targeting FAK-paxillin pathway.
26944318 In clinical samples of hepatocellular carcinom (HCC), miR-379-5p negatively correlated with FAK, which was up-regulated in HCC.
26923073 Collectively, our data demonstrate that DCMF induces cell migration and promotes wound healing through activation of Src/FAK, ERK, AKT, and p38 MAPK signaling.
26895766 Data suggest that, in colonic/prostatic neoplasm cells, increased expression of NDRG1 decreases activating phosphorylation of FAK and paxillin; silencing/inhibition of NDRG1 results in opposite effect and inhibits neoplasm cell migration/adhesion.
26892465 Data suggest that simultaneous targeting of mammalian target of rapamycin (mTOR)- and adhesion kinase (FAK)-related pathways might offer a strategy for treating acute lymphoblastic leukemia (ALL).
26833789 Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition.
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AA Sequence 

MAAAYLDPNLNHTPNSSTKTHLGTGMERSPGAMERVLKVFHYFESNSEPTTWASIIRHGDATDVRGIIQK      1 - 70
IVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHPPEEWKYELRIRYLPKGFLNQFTED     71 - 140
KPTLNFFYQQVKSDYMLEIADQVDQEIALKLGCLEIRRSYWEMRGNALEKKSNYEVLEKDVGLKRFFPKS    141 - 210
LLDSVKAKTLRKLIQQTFRQFANLNREESILKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGI    211 - 280
SYLTDKGCNPTHLADFTQVQTIQYSNSEDKDRKGMLQLKIAGAPEPLTVTAPSLTIAENMADLIDGYCRL    281 - 350
VNGTSQSFIIRPQKEGERALPSIPKLANSEKQGMRTHAVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRE    351 - 420
RIELGRCIGEGQFGDVHQGIYMSPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDHPHIVKLIGVI    421 - 490
TENPVWIIMELCTLGELRSFLQVRKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSNDCV    491 - 560
KLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMHGVKPFQGVKNND    561 - 630
VIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSRRPRFTELKAQLSTILEEEKAQQEERMRMESRRQAT    631 - 700
VSWDSGGSDEAPPKPSRPGYPSPRSSEGFYPSPQHMVQTNHYQVSGYPGSHGITAMAGSIYPGQASLLDQ    701 - 770
TDSWNHRPQEIAMWQPNVEDSTVLDLRGIGQVLPTHLMEERLIRQQQEMEEDQRWLEKEERFLKPDVRLS    771 - 840
RGSIDREDGSLQGPIGNQHIYQPVGKPDPAAPPKKPPRPGAPGHLGSLASLSSPADSYNEGVKLQPQEIS    841 - 910
PPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLALRTLLATVDETIPLLPASTH    911 - 980
REIEMAQKLLNSDLGELINKMKLAQQYVMTSLQQEYKKQMLTAAHALAVDAKNLLDVIDQARLKMLGQTR    981 - 1050
PH                                                                       1051 - 1052
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Text Mined References (702)

PMID Year Title
27009091 2016 The effects of CEP-37440, an inhibitor of focal adhesion kinase, in vitro and in vivo on inflammatory breast cancer cells.
26992741 2016 Ling Zhi-8 reduces lung cancer mobility and metastasis through disruption of focal adhesion and induction of MDM2-mediated Slug degradation.
26975850 2016 Loss of miR-203 regulates cell shape and matrix adhesion through ROBO1/Rac/FAK in response to stiffness.
26962872 2016 Focal Adhesion Kinase Inhibitors in Combination with Erlotinib Demonstrate Enhanced Anti-Tumor Activity in Non-Small Cell Lung Cancer.
26956728 2016 Bit1 knockdown contributes to growth suppression as well as the decreases of migration and invasion abilities in esophageal squamous cell carcinoma via suppressing FAK-paxillin pathway.
26944318 2016 MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma.
26923073 2016 A synthetic isoflavone, DCMF, promotes human keratinocyte migration by activating Src/FAK signaling pathway.
26895766 2016 Targeting the Metastasis Suppressor, N-Myc Downstream Regulated Gene-1, with Novel Di-2-Pyridylketone Thiosemicarbazones: Suppression of Tumor Cell Migration and Cell-Collagen Adhesion by Inhibiting Focal Adhesion Kinase/Paxillin Signaling.
26892465 2016 Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia.
26833789 2016 Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition.
More...