PTK2 - Focal adhesion kinase 1 - human protein (Function)
 
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PTK2 »  Focal adhesion kinase 1   [ EC 2.7.10.2 ]  (FADK 1)
 
Protein also known as:  Protein phosphatase 1 regulatory subunit 71 (PPP1R71).
Gene name:  PTK2
Entry whose protein(s) existence is based on evidence at protein level
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1 478 6
GENE REF ISO

Function

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Overview 
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.  
24
  • CuratedUniProtKB
Isoform  Iso 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.  
24
  • CuratedUniProtKB
GO molecular function 
Actin bindingdefinition[GO:0003779]  
1
  • IDABHF-UCL
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
JUN kinase bindingdefinition[GO:0008432]  
1
  • IDABHF-UCL
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
2
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
29
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
  • IPIHGNC
Protein kinase bindingdefinition[GO:0019901]  
1
  • IPIUniProtKB
SH2 domain bindingdefinition[GO:0042169]  
1
  • IPIUniProtKB
Signal transducer activitydefinition[GO:0004871] silver  
  • IEAInterPro 2 GO
GO biological process 
Angiogenesisdefinition[GO:0001525]  
1
  • TASUniProtKB
Axon guidancedefinition[GO:0007411]  
1
  • TASUniProtKB
Cell motilitydefinition[GO:0048870]  
1
  • TASUniProtKB
Central nervous system neuron axonogenesisdefinition[GO:0021955] silver  
  • IEAOrtholog Compara
Embryo developmentdefinition[GO:0009790]  
1
  • TASUniProtKB
Endothelial cell migrationdefinition[GO:0043542] silver  
  • IEAOrtholog Compara
Ephrin receptor signaling pathwaydefinition[GO:0048013]  
1
  • IDAUniProtKB
Establishment of cell polaritydefinition[GO:0030010]  
1
  • TASUniProtKB
Establishment of nucleus localizationdefinition[GO:0040023] silver  
  • IEAOrtholog Compara
Extracellular matrix organizationdefinition[GO:0030198] silver  
  • IEAOrtholog Compara
Growth hormone receptor signaling pathwaydefinition[GO:0060396]  
1
  • IDABHF-UCL
Heart morphogenesisdefinition[GO:0003007]  
1
  • TASUniProtKB
Integrin-mediated signaling pathwaydefinition[GO:0007229]  
2
  • TASUniProtKB
Microtubule cytoskeleton organizationdefinition[GO:0000226] silver  
  • IEAOrtholog Compara
Negative regulation of anoikisdefinition[GO:2000811]  
1
  • IMPUniProtKB
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IMPUniProtKB
Negative regulation of axonogenesisdefinition[GO:0050771] silver  
  • IEAOrtholog Compara
Negative regulation of cell-cell adhesiondefinition[GO:0022408]  
1
  • IDABHF-UCL
Negative regulation of organ growthdefinition[GO:0046621] silver  
  • IEAOrtholog Compara
Negative regulation of synapse assemblydefinition[GO:0051964] silver  
  • IEAOrtholog Compara
Netrin-activated signaling pathwaydefinition[GO:0038007]  
1
  • TASUniProtKB
Neuron migrationdefinition[GO:0001764] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
2
  • IDAUniProtKB
Placenta developmentdefinition[GO:0001890]  
1
  • TASUniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
2
  • IDABHF-UCL
  • IDAUniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284]  
  • ISSOrtholog Curator
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552]  
1
  • TASUniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • IMPUniProtKB
Positive regulation of protein kinase activitydefinition[GO:0045860]  
1
  • IMPUniProtKB
Positive regulation of protein kinase B signalingdefinition[GO:0051897]  
1
  • IMPUniProtKB
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • IMPUniProtKB
Positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic processdefinition[GO:2000060]  
  • ISSOrtholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
2
  • IDAUniProtKB
Regulation of cell adhesion mediated by integrindefinition[GO:0033628]  
1
  • IDAUniProtKB
Regulation of cell proliferationdefinition[GO:0042127]  
1
  • IMPUniProtKB
Regulation of cell shapedefinition[GO:0008360]  
2
  • IMPUniProtKB
Regulation of cytoskeleton organizationdefinition[GO:0051493]  
1
  • TASUniProtKB
Regulation of endothelial cell migrationdefinition[GO:0010594]  
1
  • TASUniProtKB
Regulation of focal adhesion assemblydefinition[GO:0051893]  
2
  • TASUniProtKB
Regulation of osteoblast differentiationdefinition[GO:0045667]  
1
  • IMPUniProtKB
Regulation of Rho GTPase activitydefinition[GO:0032319]  
1
  • TASUniProtKB
Signal complex assemblydefinition[GO:0007172] silver  
  • IEAInterPro 2 GO
Vasculogenesisdefinition[GO:0001570] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
3
  • CuratedUniProtKB
It is regulated in the following manner
Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal kinase activity. Inhibited by TAC544, TAE226, PF-573,228 and PF-562,271.  
6
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Amoebiasis  hsa05146+5747  
Axon guidance  hsa04360+5747  
Bacterial invasion of epithelial cells  hsa05100+5747  
Chemokine signaling pathway  hsa04062+5747  
ErbB signaling pathway  hsa04012+5747  
Focal adhesion  hsa04510+5747  
Leukocyte transendothelial migration  hsa04670+5747  
Pathways in cancer  hsa05200+5747  
Regulation of actin cytoskeleton  hsa04810+5747  
Small cell lung cancer  hsa05222+5747  
VEGF signaling pathway  hsa04370+5747  
According to Reactome, this protein belongs to the following pathways:
Apoptosis  REACT_578  
Cell-Cell communication  REACT_111155  
Developmental Biology  REACT_111045  
Hemostasis  REACT_604  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Molecular function 
Developmental protein  definition   [KW-0217]
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PTK2
GenomeRNAi: 5747
PRO: PR:Q05397
Chemistry
GuidetoPHARMACOLOGY: 2180