General Information of Target

Target ID LDTP06100
Target Name Protein-tyrosine kinase 2-beta (PTK2B)
Gene Name PTK2B
Gene ID 2185
Synonyms
FAK2; PYK2; RAFTK; Protein-tyrosine kinase 2-beta; EC 2.7.10.2; Calcium-dependent tyrosine kinase; CADTK; Calcium-regulated non-receptor proline-rich tyrosine kinase; Cell adhesion kinase beta; CAK-beta; CAKB; Focal adhesion kinase 2; FADK 2; Proline-rich tyrosine kinase 2; Related adhesion focal tyrosine kinase; RAFTK
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSGVSEPLSRVKLGTLRRPEGPAEPMVVVPVDVEKEDVRILKVCFYSNSFNPGKNFKLVK
CTVQTEIREIITSILLSGRIGPNIRLAECYGLRLKHMKSDEIHWLHPQMTVGEVQDKYEC
LHVEAEWRYDLQIRYLPEDFMESLKEDRTTLLYFYQQLRNDYMQRYASKVSEGMALQLGC
LELRRFFKDMPHNALDKKSNFELLEKEVGLDLFFPKQMQENLKPKQFRKMIQQTFQQYAS
LREEECVMKFFNTLAGFANIDQETYRCELIQGWNITVDLVIGPKGIRQLTSQDAKPTCLA
EFKQIRSIRCLPLEEGQAVLQLGIEGAPQALSIKTSSLAEAENMADLIDGYCRLQGEHQG
SLIIHPRKDGEKRNSLPQIPMLNLEARRSHLSESCSIESDIYAEIPDETLRRPGGPQYGI
AREDVVLNRILGEGFFGEVYEGVYTNHKGEKINVAVKTCKKDCTLDNKEKFMSEAVIMKN
LDHPHIVKLIGIIEEEPTWIIMELYPYGELGHYLERNKNSLKVLTLVLYSLQICKAMAYL
ESINCVHRDIAVRNILVASPECVKLGDFGLSRYIEDEDYYKASVTRLPIKWMSPESINFR
RFTTASDVWMFAVCMWEILSFGKQPFFWLENKDVIGVLEKGDRLPKPDLCPPVLYTLMTR
CWDYDPSDRPRFTELVCSLSDVYQMEKDIAMEQERNARYRTPKILEPTAFQEPPPKPSRP
KYRPPPQTNLLAPKLQFQVPEGLCASSPTLTSPMEYPSPVNSLHTPPLHRHNVFKRHSMR
EEDFIQPSSREEAQQLWEAEKVKMRQILDKQQKQMVEDYQWLRQEEKSLDPMVYMNDKSP
LTPEKEVGYLEFTGPPQKPPRLGAQSIQPTANLDRTDDLVYLNVMELVRAVLELKNELCQ
LPPEGYVVVVKNVGLTLRKLIGSVDDLLPSLPSSSRTEIEGTQKLLNKDLAELINKMRLA
QQNAVTSLSEECKRQMLTASHTLAVDAKNLLDAVDQAKVLANLAHPPAE
Target Type
Literature-reported
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Tyr protein kinase family, FAK subfamily
Subcellular location
Cytoplasm
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.
TTD ID
T07087
Uniprot ID
Q14289
DrugMap ID
TTTEFBV
Ensemble ID
ENST00000346049.10
HGNC ID
HGNC:9612
ChEMBL ID
CHEMBL5469

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CCK81 SNV: p.E496G DBIA    Probe Info 
D283MED SNV: p.P724S .
DU145 SNV: p.M885L DBIA    Probe Info 
HCT116 Deletion: p.V637CfsTer22 .
HEC1 SNV: p.R643W DBIA    Probe Info 
HEC1B SNV: p.M97T; p.R643W .
HUPT3 SNV: p.P645A DBIA    Probe Info 
MDAMB436 SNV: p.C395Y .
MFE319 SNV: p.L384P .
U937 Substitution: p.S9I DBIA    Probe Info 
WM793 SNV: p.K801M .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 8 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
A-EBA
 Probe Info 
50.00  LDD0214  [1]
DBIA
 Probe Info 
C89(2.35)  LDD3310  [2]
Acrolein
 Probe Info 
N.A.  LDD0221  [3]
CY-1
 Probe Info 
D369(0.00); E371(0.00); K372(0.00); Q378(0.00)  LDD0246  [4]
4-Iodoacetamidophenylacetylene
 Probe Info 
C677(0.00); C463(0.00); C89(0.00); C352(0.00)  LDD0038  [5]
IA-alkyne
 Probe Info 
C661(0.00); C463(0.00); C677(0.00); C89(0.00)  LDD0036  [5]
Lodoacetamide azide
 Probe Info 
C61(0.00); C661(0.00); C677(0.00); C89(0.00)  LDD0037  [5]
KY-26
 Probe Info 
N.A.  LDD0301  [6]
PAL-AfBPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DFG-out-3
 Probe Info 
2.70  LDD0074  [7]
DFG-out-4
 Probe Info 
3.90  LDD0075  [7]
Probe 12
 Probe Info 
N.A.  LDD0420  [8]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0165  Compound 9 HL-60 N.A.  LDD0420  [8]
 LDCM0017  DFG-out-2 A431 3.90  LDD0075  [7]
 LDCM0625  F8 Ramos C89(1.09); C61(0.54); C44(1.22); C463(1.45)  LDD2187  [9]
 LDCM0572  Fragment10 Ramos C89(1.09); C61(1.41); C44(0.71); C463(1.42)  LDD2189  [9]
 LDCM0573  Fragment11 Ramos C89(18.41); C61(4.44); C44(0.71); C463(1.46)  LDD2190  [9]
 LDCM0574  Fragment12 Ramos C89(1.07); C61(1.99); C44(0.80); C463(1.15)  LDD2191  [9]
 LDCM0575  Fragment13 Ramos C89(1.06); C61(1.09); C44(0.85); C463(0.44)  LDD2192  [9]
 LDCM0576  Fragment14 Ramos C89(0.46); C61(0.35); C44(1.16); C463(1.00)  LDD2193  [9]
 LDCM0579  Fragment20 Ramos C89(1.23); C61(1.82); C44(0.86); C562(2.23)  LDD2194  [9]
 LDCM0580  Fragment21 Ramos C89(0.96); C61(1.00); C44(0.92); C463(0.90)  LDD2195  [9]
 LDCM0582  Fragment23 Ramos C89(1.04); C61(1.45); C44(0.97); C463(0.94)  LDD2196  [9]
 LDCM0578  Fragment27 Ramos C89(1.00); C61(1.04); C44(1.12); C463(1.39)  LDD2197  [9]
 LDCM0586  Fragment28 Ramos C89(1.00); C61(0.73); C44(0.53); C463(0.62)  LDD2198  [9]
 LDCM0588  Fragment30 Ramos C89(1.13); C61(1.60); C44(1.04); C463(0.81)  LDD2199  [9]
 LDCM0589  Fragment31 Ramos C89(0.97); C61(1.00); C44(0.88); C463(0.67)  LDD2200  [9]
 LDCM0590  Fragment32 Ramos C89(0.74); C61(1.08); C44(0.59); C463(2.01)  LDD2201  [9]
 LDCM0468  Fragment33 Ramos C89(0.96); C61(1.19); C44(0.74); C463(0.99)  LDD2202  [9]
 LDCM0596  Fragment38 Ramos C89(0.96); C61(1.18); C44(0.75); C463(1.45)  LDD2203  [9]
 LDCM0566  Fragment4 Ramos C89(1.03); C61(0.64); C44(0.85); C463(0.84)  LDD2184  [9]
 LDCM0610  Fragment52 Ramos C89(2.08); C61(1.75); C44(1.11); C463(1.02)  LDD2204  [9]
 LDCM0614  Fragment56 Ramos C89(1.26); C61(1.51); C44(0.99); C463(1.09)  LDD2205  [9]
 LDCM0569  Fragment7 Ramos C89(1.13); C61(0.92); C44(0.90); C463(1.22)  LDD2186  [9]
 LDCM0571  Fragment9 Ramos C89(1.70); C61(2.13); C44(1.15); C463(1.48)  LDD2188  [9]
 LDCM0107  IAA HeLa N.A.  LDD0221  [3]
 LDCM0022  KB02 Ramos C89(1.64); C61(0.56); C44(0.80); C463(1.36)  LDD2182  [9]
 LDCM0023  KB03 Jurkat C972(4.51)  LDD0315  [10]
 LDCM0024  KB05 COLO792 C89(2.35)  LDD3310  [2]
 LDCM0131  RA190 MM1.R C899(1.92); C972(1.77); C677(1.28); C44(1.10)  LDD0304  [11]
 LDCM0016  Ranjitkar_cp1 A431 2.70  LDD0074  [7]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Proto-oncogene tyrosine-protein kinase Src (SRC) Tyr protein kinase family P12931
Tyrosine-protein kinase Fyn (FYN) Tyr protein kinase family P06241
Rho-related GTP-binding protein RhoU (RHOU) Rho family Q7L0Q8
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Amyloid-beta precursor protein (APP) APP family P05067
Other
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Nephrocystin-1 (NPHP1) Nephrocystin-1 family O15259
Nephrocystin-4 (NPHP4) NPHP4 family O75161

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fostamatinib Small molecular drug DB12010
Leflunomide Small molecular drug DB01097
Investigative
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Aloisine Small molecular drug D00SEC
Genistein Small molecular drug DB01645
4-{[4-{[(1r2r)-2-(Dimethylamino)Cyclopentyl]Amino}-5-(Trifluoromethyl)Pyrimidin-2-yl]Amino}-n-methylbenzenesulfonamide . DB08341

References

1 2-Ethynylbenzaldehyde-Based, Lysine-Targeting Irreversible Covalent Inhibitors for Protein Kinases and Nonkinases. J Am Chem Soc. 2023 Feb 12. doi: 10.1021/jacs.2c11595. Online ahead of print.
Mass spectrometry data entry: PXD037665
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
3 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
4 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
5 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
6 Direct Target Site Identification of a Sulfonyl-Triazole Covalent Kinase Probe by LC-MS Chemical Proteomics. Anal Chem. 2021 Sep 7;93(35):11946-11955. doi: 10.1021/acs.analchem.1c01591. Epub 2021 Aug 25.
7 Affinity-based probes based on type II kinase inhibitors. J Am Chem Soc. 2012 Nov 21;134(46):19017-25. doi: 10.1021/ja306035v. Epub 2012 Nov 6.
8 A Photoaffinity Displacement Assay and Probes to Study the Cyclin-Dependent Kinase Family. Angew Chem Int Ed Engl. 2019 Nov 25;58(48):17322-17327. doi: 10.1002/anie.201906321. Epub 2019 Oct 31.
9 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
10 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
11 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell Chem Biol. 2020 Nov 19;27(11):1371-1382.e6. doi: 10.1016/j.chembiol.2020.08.007. Epub 2020 Aug 27.