Details of the Target

General Information of Target

Target ID LDTP03478
Target Name Tyrosine-protein phosphatase non-receptor type 6 (PTPN6)
Gene Name PTPN6
Gene ID 5777
Synonyms
HCP; PTP1C; Tyrosine-protein phosphatase non-receptor type 6; EC 3.1.3.48; Hematopoietic cell protein-tyrosine phosphatase; Protein-tyrosine phosphatase 1C; PTP-1C; Protein-tyrosine phosphatase SHP-1; SH-PTP1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDF
YDLYGGEKFATLTELVEYYTQQQGVLQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQA
ETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGG
LETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTA
KAGFWEEFESLQKQEVKNLHQRLEGQRPENKGKNRYKNILPFDHSRVILQGRDSNIPGSD
YINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNK
CVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDH
GVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDC
DIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNIT
YPPAMKNAHAKASRTSSKHKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRK
Target Type
Patented-recorded
Target Bioclass
Enzyme
Family
Protein-tyrosine phosphatase family, Non-receptor class 2 subfamily
Subcellular location
Cytoplasm
Function
Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.
TTD ID
T98264
Uniprot ID
P29350
DrugMap ID
TT369M5
Ensemble ID
ENST00000318974.14
HGNC ID
HGNC:9658
ChEMBL ID
CHEMBL3166

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A3KAW SNV: p.P105L; p.D419G DBIA    Probe Info 
CAOV3 Deletion: p.N381TfsTer25 DBIA    Probe Info 
CHL1 SNV: p.N343T .
HCC1143 SNV: p.D8Y DBIA    Probe Info 
JURKAT Substitution: p.N278Y Compound 10    Probe Info 
MOLT4 SNV: p.M470T; p.Y509Ter; p.L592H IA-alkyne    Probe Info 
REH Deletion: p.E384SfsTer22 DBIA    Probe Info 
SNU1 SNV: p.T165A; p.R352Ter .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 11 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
Probe 1
 Probe Info  		Y64(8.06); Y214(124.09); Y301(9.76); Y536(8.55)  LDD3495  [1]
DBIA
 Probe Info  		C482(1.82); C173(1.13)  LDD3310  [2]
4-Iodoacetamidophenylacetylene
 Probe Info  		C382(0.00); C361(0.00); C480(0.00); C453(0.00)  LDD0038  [3]
IA-alkyne
 Probe Info  		C382(0.00); C361(0.00); C480(0.00); C453(0.00)  LDD0036  [3]
IPIAA_L
 Probe Info  		C480(0.00); C382(0.00)  LDD0031  [4]
Lodoacetamide azide
 Probe Info  		C382(0.00); C361(0.00); C480(0.00); C453(0.00)  LDD0037  [3]
WYneN
 Probe Info  		N.A.  LDD0021  [5]
Compound 10
 Probe Info  		N.A.  LDD2216  [6]
Compound 11
 Probe Info  		N.A.  LDD2213  [6]
TFBX
 Probe Info  		N.A.  LDD0148  [7]
NAIA_5
 Probe Info  		N.A.  LDD2223  [8]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
VE-P
 Probe Info  		N.A.  LDD0396  [9]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 22RV1 C173(1.24); C63(1.31)  LDD2243  [2]
 LDCM0023  KB03 22RV1 C173(1.38); C63(1.65)  LDD2660  [2]
 LDCM0024  KB05 COLO792 C482(1.82); C173(1.13)  LDD3310  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Caspase-8 (CASP8) Peptidase C14A family Q14790
Vascular endothelial growth factor receptor 2 (KDR) Tyr protein kinase family P35968
Focal adhesion kinase 1 (PTK2) Tyr protein kinase family Q05397
Insulin-like growth factor 1 receptor (IGF1R) Tyr protein kinase family P08069
Proto-oncogene tyrosine-protein kinase ROS (ROS1) Tyr protein kinase family P08922
Tyrosine-protein kinase Lck (LCK) Tyr protein kinase family P06239
Immunoglobulin
Click To Hide/Show 13 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) Immunoglobulin superfamily P43626
Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3) Immunoglobulin superfamily P43628
B-cell receptor CD22 (CD22) SIGLEC (sialic acid binding Ig-like lectin) family P20273
Myeloid cell surface antigen CD33 (CD33) SIGLEC (sialic acid binding Ig-like lectin) family P20138
Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) . Q8NHL6
Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) . Q8N423
Leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3) . O75022
Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4) . Q8NHJ6
Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) . Q6GTX8
Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B) . P31994
Natural killer cell receptor 2B4 (CD244) . Q9BZW8
Paired immunoglobulin-like type 2 receptor alpha (PILRA) . Q9UKJ1
Platelet endothelial cell adhesion molecule (PECAM1) . P16284
Cytokine and receptor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Erythropoietin receptor (EPOR) Type I cytokine receptor family P19235
Other
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) ATG8 family Q9H492
Growth factor receptor-bound protein 2 (GRB2) GRB2/sem-5/DRK family P62993
Leukocyte antigen CD37 (CD37) Tetraspanin (TM4SF) family P11049
Protein THEMIS (THEMIS) Themis family Q8N1K5
Four and a half LIM domains protein 3 (FHL3) . Q13643

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Tiludronic Acid Small molecular drug DB01133
Patented
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bdbm50054344 Small molecular drug D0I2AN
Nsc-87877 Small molecular drug D00MFW

References

1 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
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 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
4 SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines. Mol Cell Proteomics. 2022 Apr;21(4):100218. doi: 10.1016/j.mcpro.2022.100218. Epub 2022 Feb 25.
Mass spectrometry data entry: PXD029500 , PXD031647
5 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
6 Multiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling. Anal Chem. 2021 Feb 2;93(4):2610-2618. doi: 10.1021/acs.analchem.0c04726. Epub 2021 Jan 20.
Mass spectrometry data entry: PXD022279
7 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
8 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
9 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.