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  6. FAK family
  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. [provided by RefSeq, Jun 2017]

 Comments

Property Summary

Ligand Count 304
NCBI Gene PubMed Count 745
PubMed Score 1038.29
PubTator Score 1563.61

Knowledge Summary

Patent (30,498)

TINX Plot

  Disease (5)

Disease Target Count Z-score Confidence
Carcinoma 11493 0.0 1.1
Kidney cancer 2613 0.0 0.5
Disease Target Count Z-score Confidence
Cancer 2499 5.745 2.9

Expression

  Differential Expression (13)

Disease log2 FC p
Breast cancer 1.100 2.0e-05
intraductal papillary-mucinous adenoma (... 1.900 4.0e-04
intraductal papillary-mucinous carcinoma... 2.100 7.6e-04
intraductal papillary-mucinous neoplasm ... 1.900 3.9e-03
mucosa-associated lymphoid tissue lympho... 1.093 5.5e-03
non-small cell lung cancer 1.474 5.2e-16
oligodendroglioma 1.400 1.2e-03
osteosarcoma 3.008 3.0e-06
ovarian cancer 1.400 3.0e-03
pancreatic ductal adenocarcinoma liver m... 1.598 1.0e-03
Pick disease -1.200 1.1e-05
spina bifida -2.555 3.9e-02
subependymal giant cell astrocytoma -1.974 4.5e-03

Synonym

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

Gene

PTK2

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 (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (24)

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 GO Function (11)

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 GO Component (12)

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 GO Process (53)

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 Compartment GO Term (84)

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 MGI Phenotype (18)

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 GWAS Trait (2)

 HCA RNA Cell Line (56)

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Pathway (126)

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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

Gene RIF (596)

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
//

Text Mined References (779)

PMID Year Title