Human Gene PTK2 (ENST00000395218.3) Description and Page Index

Description: 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. (from UniProt Q05397)
Gencode Transcript: ENST00000395218.3
Gencode Gene: ENSG00000169398.19
Transcript (Including UTRs)
Position: hg38 chr8:140,658,382-141,001,313 Size: 342,932 Total Exon Count: 31 Strand: -
Coding Region
Position: hg38 chr8:140,659,466-140,890,737 Size: 231,272 Coding Exon Count: 29

Page Index

Sequence and Links

UniProtKB Comments

Protein Structure

Other Names

Methods

Data last updated at UCSC: 2021-06-20 19:51:40

Comments and Description Text from UniProtKB


	ID: FAK1_HUMAN DESCRIPTION: RecName: Full=Focal adhesion kinase 1; Short=FADK 1; EC=2.7.10.2; AltName: Full=Focal adhesion kinase-related nonkinase; Short=FRNK; AltName: Full=Protein phosphatase 1 regulatory subunit 71; Short=PPP1R71; AltName: Full=Protein-tyrosine kinase 2; AltName: Full=p125FAK; AltName: Full=pp125FAK; 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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: 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. SUBUNIT: 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). INTERACTION: P29317:EPHA2; NbExp=3; IntAct=EBI-702142, EBI-702104; Q9Y3E5:PTRH2; NbExp=2; IntAct=EBI-702142, EBI-1056751; P49023:PXN; NbExp=13; IntAct=EBI-702142, EBI-702209; P12931:SRC; NbExp=4; IntAct=EBI-702142, EBI-621482; Q62219:Tgfb1i1 (xeno); NbExp=3; IntAct=EBI-702142, EBI-642844; Q68CZ2:TNS3; NbExp=3; IntAct=EBI-702142, EBI-1220488; P04637:TP53; NbExp=11; IntAct=EBI-702142, EBI-366083; SUBCELLULAR LOCATION: Cell junction, focal adhesion. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cell cortex. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, centrosome (By similarity). Nucleus. Note=Constituent of focal adhesions. Detected at microtubules. TISSUE SPECIFICITY: Detected in B and T-lymphocytes. Isoform 1 and isoform 6 are detected in lung fibroblasts (at protein level). Ubiquitous. DEVELOPMENTAL STAGE: Isoform 6 is detected in cultured cells, immediately after seeding and before formation of focal adhesions (at protein level). DOMAIN: The Pro-rich regions interact with the SH3 domain of CAS family members, such as BCAR1 and NEDD9, and with the GTPase activating protein ARHGAP26. DOMAIN: The carboxy-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions. PTM: Phosphorylated on tyrosine residues upon activation, e.g. upon integrin signaling. Tyr-397 is the major autophosphorylation site, but other kinases can also phosphorylate this residue. Phosphorylation at Tyr-397 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER promotes phosphorylation at Tyr-577, Tyr- 861 and Tyr-925, even when cells are not adherent. Tyr-397, Tyr- 576 and Ser-722 are phosphorylated only when cells are adherent. Phosphorylation at Tyr-397 is important for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-925 is important for interaction with GRB2. Dephosphorylated by PTPN11; PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated). Microtubule-induced dephosphorylation at Tyr-397 is crucial for the induction of focal adhesion disassembly; this dephosphorylation could be catalyzed by PTPN11 and regulated by ZFYVE21. PTM: Sumoylated; this enhances autophosphorylation (By similarity). DISEASE: 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. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily. SIMILARITY: Contains 1 FERM domain. SIMILARITY: Contains 1 protein kinase domain.