DegronMD - Q14289(PTK2B)

FUNCTION: Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. 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 of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}. View more >>

GO - Biological processes (BP): activation of GTPase activity [GO:0090630]; activation of Janus kinase activity [GO:0042976]; adaptive immune response [GO:0002250]; apoptotic process [GO:0006915]; blood vessel endothelial cell migration [GO:0043534]; bone resorption [GO:0045453]; cell differentiation [GO:0030154]; cell surface receptor signaling pathway [GO:0007166]; cellular defense response [GO:0006968]; cellular response to fluid shear stress [GO:0071498]; cellular response to retinoic acid [GO:0071300]; chemokine-mediated signaling pathway [GO:0070098]; endothelin receptor signaling pathway [GO:0086100]; epidermal growth factor receptor signaling pathway [GO:0007173]; focal adhesion assembly [GO:0048041]; glial cell proliferation [GO:0014009]; innate immune response [GO:0045087]; integrin-mediated signaling pathway [GO:0007229]; ionotropic glutamate receptor signaling pathway [GO:0035235]; long-term synaptic depression [GO:0060292]; long-term synaptic potentiation [GO:0060291]; MAPK cascade [GO:0000165]; marginal zone B cell differentiation [GO:0002315]; negative regulation of apoptotic process [GO:0043066]; negative regulation of bone mineralization [GO:0030502]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of muscle cell apoptotic process [GO:0010656]; negative regulation of myeloid cell differentiation [GO:0045638]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of potassium ion transport [GO:0043267]; neuron projection development [GO:0031175]; oocyte maturation [GO:0001556]; peptidyl-tyrosine autophosphorylation [GO:0038083]; peptidyl-tyrosine phosphorylation [GO:0018108]; positive regulation of actin filament polymerization [GO:0030838]; positive regulation of angiogenesis [GO:0045766]; positive regulation of B cell chemotaxis [GO:2000538]; positive regulation of cell growth [GO:0030307]; positive regulation of cell-matrix adhesion [GO:0001954]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of DNA biosynthetic process [GO:2000573]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of excitatory postsynaptic potential [GO:2000463]; positive regulation of JNK cascade [GO:0046330]; positive regulation of JUN kinase activity [GO:0043507]; positive regulation of neuron projection development [GO:0010976]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of nitric-oxide synthase activity [GO:0051000]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of phosphatidylinositol 3-kinase activity [GO:0043552]; positive regulation of protein kinase activity [GO:0045860]; positive regulation of reactive oxygen species metabolic process [GO:2000379]; positive regulation of synaptic transmission, glutamatergic [GO:0051968]; positive regulation of translation [GO:0045727]; positive regulation of ubiquitin-dependent protein catabolic process [GO:2000060]; protein autophosphorylation [GO:0046777]; protein-containing complex assembly [GO:0065003]; protein phosphorylation [GO:0006468]; regulation of actin cytoskeleton reorganization [GO:2000249]; regulation of calcium-mediated signaling [GO:0050848]; regulation of cell adhesion [GO:0030155]; regulation of cell shape [GO:0008360]; regulation of cGMP-mediated signaling [GO:0010752]; regulation of establishment of cell polarity [GO:2000114]; regulation of inositol trisphosphate biosynthetic process [GO:0032960]; regulation of macrophage chemotaxis [GO:0010758]; regulation of NMDA receptor activity [GO:2000310]; regulation of release of sequestered calcium ion into cytosol [GO:0051279]; regulation of synaptic plasticity [GO:0048167]; regulation of ubiquitin-dependent protein catabolic process [GO:2000058]; response to calcium ion [GO:0051592]; response to cAMP [GO:0051591]; response to cation stress [GO:0043157]; response to cocaine [GO:0042220]; response to ethanol [GO:0045471]; response to glucose [GO:0009749]; response to hormone [GO:0009725]; response to hydrogen peroxide [GO:0042542]; response to hypoxia [GO:0001666]; response to immobilization stress [GO:0035902]; response to ischemia [GO:0002931]; response to lithium ion [GO:0010226]; response to mechanical stimulus [GO:0009612]; response to xenobiotic stimulus [GO:0009410]; signal complex assembly [GO:0007172]; signal transduction [GO:0007165]; sprouting angiogenesis [GO:0002040]; stress fiber assembly [GO:0043149]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]; tumor necrosis factor-mediated signaling pathway [GO:0033209]; 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.E6D	TCGA-42-2589	OV	TCGA	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.25
p.E6D	DO31130	OV	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.25
p.E6K	TCGA-73-4676	LUAD	TCGA	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.25
p.E6K	DO24810	LUAD	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.25
p.H365Y	TCGA-86-8358	LUAD	TCGA	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.1389
p.R18W	TCGA-AB-2828	LAML	TCGA	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.3056
p.R18W	DO21571	LAML	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.3056
p.L13S	TCGA-AP-A0LM	UCEC	TCGA	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7667
p.L13S	DO43306	UCEC	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7667
p.P19S	TCGA-AX-A2HD	UCEC	TCGA	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.2778
p.P19S	DO42608	UCEC	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.2778
p.R373W	TCGA-B5-A3FA	UCEC	TCGA	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation altering degron motif	0.8634
p.R373W	TCGA-BB-A5HU	HNSC	TCGA	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation altering degron motif	0.8634
p.R373W	TCGA-EY-A1GI	UCEC	TCGA	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation altering degron motif	0.8634
p.M832T	TCGA-B5-A3FA	UCEC	TCGA	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.1111
p.E371D	TCGA-DA-A1IB	SKCM	TCGA	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.3056
p.L384M	TCGA-DF-A2KN	UCEC	TCGA	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.2222
p.L384M	DO233944	GACA	ICGC	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.2222
p.L384M	DO223282	UCEC	ICGC	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.2222
p.G854W	TCGA-DF-A2KN	UCEC	TCGA	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.1111
p.G854W	DO223282	UCEC	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.1111
p.E846D	TCGA-EE-A17Z	SKCM	TCGA	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation altering degron motif	0.6758
p.P22H	TCGA-ER-A19T	SKCM	TCGA	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.1944
p.P22H	DO51251	SKCM	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.1944
p.G370S	TCGA-ET-A4KN	THCA	TCGA	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.2778
p.G370S	DO39072	THCA	ICGC	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.2778
p.G2R	DO222973	BTCA	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation blocking phosphorylation signal	0.5833
p.F852L	DO10172	COAD	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.1667
p.R389Q	DO234250	ESAD	ICGC	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.0833
p.R847W	DO15671	HNSC	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.3056
p.R847W	DO228138	PBCA	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.3056
p.S9I	DO229018	LICA	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7341
p.S9I	SIDM01205	Acute Myeloid Leukemia	GDSC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7341
p.S9I	SIDM01195	Acute Myeloid Leukemia	GDSC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7341
p.S9I	ACH-002314	Leukemia	CCLE	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7341
p.S9I	TUR	haematopoietic and lymphoid tissue	COSMIC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7341
p.G2W	DO26746	LUSC	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation blocking phosphorylation signal	0.5833
p.T4A	DO228371	MALY	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.1944
p.V833F	DO232842	NACA	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.1389
p.R18Q	DO233292	NACA	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.3056
p.Q9H	DO220065	SARC	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7582
p.A848V	DO37667	SKCM	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.2778
p.A848S	DO37703	SKCM	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.2778
p.L12I	DO37431	SKCM	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7174
p.E851K	DO50118	STAD	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation rewiring degron network	0.1944
p.K853N	DO219773	UCEC	ICGC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation blocking phosphorylation signal	0.5833
p.N20D	DO42673	UCEC	ICGC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.25
p.T842M	SIDM00578	Neuroblastoma	GDSC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation altering degron motif	0.8534
p.T842M	NB1	autonomic ganglia	COSMIC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation altering degron motif	0.8534
p.R18L	SIDM00810	Non-Small Cell Lung Carcinoma	GDSC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.3056
p.R18L	ACH-000757	Lung Cancer	CCLE	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.3056
p.R18L	A427	lung	COSMIC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation rewiring degron network	0.3056
p.R10Q	SIDM00343	Glioblastoma	GDSC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7329
p.R10Q	LN-405	central nervous system	COSMIC	SRVKLGTLR	DEG_APCC_DBOX_1	9:17	Mutation altering degron motif	0.7329
p.N383K	SIDM00674	Non-Cancerous	GDSC	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.25
p.R388Q	SIDM00254	Neuroblastoma	GDSC	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.1111
p.R373L	SIDM00542	Glioblastoma	GDSC	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation altering degron motif	0.8428
p.R373L	ACH-002227	Brain Cancer	CCLE	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation altering degron motif	0.8428
p.R373L	D-392MG	central nervous system	COSMIC	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation altering degron motif	0.8428
p.L384P	ACH-000988	Endometrial/Uterine Cancer	CCLE	KRNSLPQIP	DEG_APCC_DBOX_1	372:380	Mutation rewiring degron network	0.2222
p.N841S	SUP-B15	haematopoietic and lymphoid tissue	COSMIC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation altering degron motif	0.7069
p.N841S	H3255	lung	COSMIC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation altering degron motif	0.7069
p.M843L	DU-145	prostate	COSMIC	PLTPEKE	DEG_SCF_FBW7_2	840:846	Mutation altering degron motif	0.711

Kaplan plot for PTK2B in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

PTK2B

UniProt ID: Q14289

Entrez ID: 2185

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PTK2B in