DegronMD - Q05397(PTK2)

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. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698}.; FUNCTION: [Isoform 6]: 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. {ECO:0000269|PubMed:20109444}. View more >>

GO - Biological processes (BP): angiogenesis [GO:0001525]; axon guidance [GO:0007411]; cell differentiation [GO:0030154]; cell migration [GO:0016477]; cell motility [GO:0048870]; detection of muscle stretch [GO:0035995]; ephrin receptor signaling pathway [GO:0048013]; epidermal growth factor receptor signaling pathway [GO:0007173]; establishment of cell polarity [GO:0030010]; Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096]; growth hormone receptor signaling pathway [GO:0060396]; heart morphogenesis [GO:0003007]; innate immune response [GO:0045087]; integrin-mediated signaling pathway [GO:0007229]; negative regulation of anoikis [GO:2000811]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell-cell adhesion [GO:0022408]; netrin-activated signaling pathway [GO:0038007]; peptidyl-tyrosine phosphorylation [GO:0018108]; placenta development [GO:0001890]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of fibroblast migration [GO:0010763]; positive regulation of macrophage chemotaxis [GO:0010759]; positive regulation of macrophage proliferation [GO:0120041]; positive regulation of phosphatidylinositol 3-kinase activity [GO:0043552]; positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068]; positive regulation of protein kinase activity [GO:0045860]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of ubiquitin-dependent protein catabolic process [GO:2000060]; positive regulation of wound healing [GO:0090303]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; regulation of cell adhesion [GO:0030155]; regulation of cell adhesion mediated by integrin [GO:0033628]; regulation of cell population proliferation [GO:0042127]; regulation of cell shape [GO:0008360]; regulation of cytoskeleton organization [GO:0051493]; regulation of endothelial cell migration [GO:0010594]; regulation of epithelial cell migration [GO:0010632]; regulation of focal adhesion assembly [GO:0051893]; regulation of GTPase activity [GO:0043087]; regulation of osteoblast differentiation [GO:0045667]; regulation of protein phosphorylation [GO:0001932]; regulation of substrate adhesion-dependent cell spreading [GO:1900024]; signal complex assembly [GO:0007172]; transforming growth factor beta receptor signaling pathway [GO:0007179]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]; vascular endothelial growth factor receptor signaling pathway [GO:0048010] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.L6V	TCGA-29-1698	OV	TCGA	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation blocking phosphorylation signal	0.6667
p.L6V	TCGA-29-1698	OV	TCGA	PNSST	DEG_SPOP_SBC_1	14:18	Mutation blocking phosphorylation signal	0.5556
p.L6V	DO28531	OV	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation blocking phosphorylation signal	0.6667
p.L6V	DO28531	OV	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation blocking phosphorylation signal	0.5556
p.R28C	TCGA-A5-A0G2	UCEC	TCGA	PNSST	DEG_SPOP_SBC_1	14:18	Mutation rewiring degron network	0.0556
p.R28C	DO41235	UCEC	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation rewiring degron network	0.0556
p.S16L	TCGA-AP-A1E0	UCEC	TCGA	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	TCGA-AP-A1E0	UCEC	TCGA	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	TCGA-D1-A16X	UCEC	TCGA	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	TCGA-D1-A16X	UCEC	TCGA	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	TCGA-E6-A1LX	UCEC	TCGA	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	TCGA-E6-A1LX	UCEC	TCGA	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	DO8730	COAD	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	DO8730	COAD	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	DO41020	UCEC	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	DO41020	UCEC	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	DO43154	UCEC	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	DO43154	UCEC	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	DO41799	UCEC	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	DO41799	UCEC	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	SIDM01043	Other Sarcomas	GDSC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	SIDM01043	Other Sarcomas	GDSC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	ACH-000913	Endometrial/Uterine Cancer	CCLE	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	ACH-000913	Endometrial/Uterine Cancer	CCLE	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.S16L	ESS-1	endometrium	COSMIC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7667
p.S16L	ESS-1	endometrium	COSMIC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.8778
p.A2T	TCGA-CM-5861	COAD	TCGA	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation blocking phosphorylation signal	0.5556
p.A2T	DO7918	COAD	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation blocking phosphorylation signal	0.5556
p.H12Y	TCGA-IR-A3LA	CESC	TCGA	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.6118
p.H12Y	DO44377	CESC	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.6118
p.P14T	TCGA-IS-A3KA	SARC	TCGA	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7031
p.P14T	TCGA-IS-A3KA	SARC	TCGA	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.7031
p.P14T	DO220172	SARC	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7031
p.P14T	DO220172	SARC	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.7031
p.S15F	DO51925	BLCA	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7982
p.S15F	DO51925	BLCA	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.7982
p.S11Y	DO457	BLCA	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.712
p.I14K	DO227987	COCA	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7531
p.I14K	DO227987	COCA	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.7531
p.Y12H	DO224761	COCA	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.7229
p.P25S	DO50357	ESAD	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation rewiring degron network	0.1111
p.P25S	DO50357	ESAD	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation rewiring degron network	0.1389
p.D7G	DO233089	GACA	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation rewiring degron network	0.25
p.D7G	DO233089	GACA	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation rewiring degron network	0.1389
p.R28S	DO229041	LICA	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation rewiring degron network	0.0556
p.E9D	DO229044	LICA	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation blocking phosphorylation signal	0.6389
p.S15Y	DO46657	PAAD	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.712
p.S15Y	DO46657	PAAD	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.712
p.S17Y	DO41133	UCEC	ICGC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.712
p.S17Y	DO41133	UCEC	ICGC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.712
p.P8S	SIDM01629	Melanoma	GDSC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation substituting flanking lysine	0.2778
p.P8S	ACH-000404	Skin Cancer	CCLE	PNSST	DEG_SPOP_SBC_1	14:18	Mutation substituting flanking lysine	0.2778
p.N15S	Daudi	haematopoietic and lymphoid tissue	COSMIC	LNHTPNSS	DEG_SCF_FBW7_1	10:17	Mutation altering degron motif	0.5958
p.N15S	Daudi	haematopoietic and lymphoid tissue	COSMIC	PNSST	DEG_SPOP_SBC_1	14:18	Mutation altering degron motif	0.5958

Kaplan plot for PTK2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PTK2

UniProt ID: Q05397

Entrez ID: 5747

Protein name: Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PTK2 in