Details of the Target

General Information of Target

Target ID LDTP07286
Target Name Tensin-2 (TNS2)
Gene Name TNS2
Gene ID 23371
Synonyms
KIAA1075; TENC1; Tensin-2; EC 3.1.3.48; C1 domain-containing phosphatase and tensin homolog; C1-TEN; Tensin-like C1 domain-containing phosphatase
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MKSSGPVERLLRALGRRDSSRAASRPRKAEPHSFREKVFRKKPPVCAVCKVTIDGTGVSC
RVCKVATHRKCEAKVTSACQALPPVELRRNTAPVRRIEHLGSTKSLNHSKQRSTLPRSFS
LDPLMERRWDLDLTYVTERILAAAFPARPDEQRHRGHLRELAHVLQSKHRDKYLLFNLSE
KRHDLTRLNPKVQDFGWPELHAPPLDKLCSICKAMETWLSADPQHVVVLYCKGNKGKLGV
IVSAYMHYSKISAGADQALATLTMRKFCEDKVATELQPSQRRYISYFSGLLSGSIRMNSS
PLFLHYVLIPMLPAFEPGTGFQPFLKIYQSMQLVYTSGVYHIAGPGPQQLCISLEPALLL
KGDVMVTCYHKGGRGTDRTLVFRVQFHTCTIHGPQLTFPKDQLDEAWTDERFPFQASVEF
VFSSSPEKIKGSTPRNDPSVSVDYNTTEPAVRWDSYENFNQHHEDSVDGSLTHTRGPLDG
SPYAQVQRPPRQTPPAPSPEPPPPPMLSVSSDSGHSSTLTTEPAAESPGRPPPTAAERQE
LDRLLGGCGVASGGRGAGRETAILDDEEQPTVGGGPHLGVYPGHRPGLSRHCSCRQGYRE
PCGVPNGGYYRPEGTLERRRLAYGGYEGSPQGYAEASMEKRRLCRSLSEGLYPYPPEMGK
PATGDFGYRAPGYREVVILEDPGLPALYPCPACEEKLALPTAALYGLRLEREAGEGWASE
AGKPLLHPVRPGHPLPLLLPACGHHHAPMPDYSCLKPPKAGEEGHEGCSYTMCPEGRYGH
PGYPALVTYSYGGAVPSYCPAYGRVPHSCGSPGEGRGYPSPGAHSPRAGSISPGSPPYPQ
SRKLSYEIPTEEGGDRYPLPGHLASAGPLASAESLEPVSWREGPSGHSTLPRSPRDAPCS
ASSELSGPSTPLHTSSPVQGKESTRRQDTRSPTSAPTQRLSPGEALPPVSQAGTGKAPEL
PSGSGPEPLAPSPVSPTFPPSSPSDWPQERSPGGHSDGASPRSPVPTTLPGLRHAPWQGP
RGPPDSPDGSPLTPVPSQMPWLVASPEPPQSSPTPAFPLAASYDTNGLSQPPLPEKRHLP
GPGQQPGPWGPEQASSPARGISHHVTFAPLLSDNVPQTPEPPTQESQSNVKFVQDTSKFW
YKPHLSRDQAIALLKDKDPGAFLIRDSHSFQGAYGLALKVATPPPSAQPWKGDPVEQLVR
HFLIETGPKGVKIKGCPSEPYFGSLSALVSQHSISPISLPCCLRIPSKDPLEETPEAPVP
TNMSTAADLLRQGAACSVLYLTSVETESLTGPQAVARASSAALSCSPRPTPAVVHFKVSA
QGITLTDNQRKLFFRRHYPVNSITFSSTDPQDRRWTNPDGTTSKIFGFVAKKPGSPWENV
CHLFAELDPDQPAGAIVTFITKVLLGQRK
Target Bioclass
Enzyme
Family
PTEN phosphatase protein family
Subcellular location
Cell junction, focal adhesion
Function
Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin. Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain. In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy. Negatively regulates PI3K-AKT pathway activation. Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of the mTORC1 complex. Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K) which balances mTORC1 activity but high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria. Required for correct podocyte morphology, podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier. Enhances RHOA activation in the presence of DLC1. Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix.
Uniprot ID
Q63HR2
Ensemble ID
ENST00000314250.11
HGNC ID
HGNC:19737

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
FADU SNV: p.V509I .
HCT116 Deletion: p.M506CfsTer14 .
HS936T Substitution: p.S279F .
HT SNV: p.E405A .
LNCaP clone FGC SNV: p.T134A .
MDAMB453 SNV: p.E419K .
MEWO SNV: p.P399S DBIA    Probe Info 
MFE319 SNV: p.V364I .
NCIH2122 SNV: p.L124P .
RL952 SNV: p.G553E .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C819(1.38)  LDD3312  [1]
NAIA_4
 Probe Info  		N.A.  LDD2226  [2]
IPM
 Probe Info  		C899(0.00); C548(0.00)  LDD0147  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A204 C1315(1.56)  LDD2252  [1]
 LDCM0023  KB03 MDA-MB-231 C548(0.81)  LDD1701  [4]
 LDCM0024  KB05 HMCB C819(1.38)  LDD3312  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 11 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Fatty acid desaturase 6 (FADS6) Fatty acid desaturase type 1 family Q8N9I5
Cathepsin Z (CTSZ) Peptidase C1 family Q9UBR2
Hepatocyte growth factor receptor (MET) Tyr protein kinase family P08581
Mast/stem cell growth factor receptor Kit (KIT) Tyr protein kinase family P10721
Receptor tyrosine-protein kinase erbB-2 (ERBB2) Tyr protein kinase family P04626
Receptor tyrosine-protein kinase erbB-3 (ERBB3) Tyr protein kinase family P21860
Tensin-2 (TNS2) PTEN phosphatase protein family Q63HR2
Terminal nucleotidyltransferase 5B (TENT5B) TENT family Q96A09
E3 ubiquitin-protein ligase TRIM8 (TRIM8) TRIM/RBCC family Q9BZR9
E3 ubiquitin-protein ligase DZIP3 (DZIP3) . Q86Y13
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) . Q13526
Transporter and channel
Click To Hide/Show 7 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Metal transporter CNNM3 (CNNM3) ACDP family Q8NE01
ATP synthase subunit delta, mitochondrial (ATP5F1D) ATPase epsilon chain family P30049
Cation channel sperm-associated protein 1 (CATSPER1) Cation channel sperm-associated (TC 1.A.1.19) family Q8NEC5
Receptor expression-enhancing protein 6 (REEP6) DP1 family Q96HR9
Cilium assembly protein DZIP1 (DZIP1) DZIP C2H2-type zinc-finger protein family Q86YF9
Aquaporin-1 (AQP1) MIP/aquaporin (TC 1.A.8) family P29972
Phospholipid scramblase 3 (PLSCR3) Phospholipid scramblase family Q9NRY6
Transcription factor
Click To Hide/Show 21 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Homeobox protein Hox-B9 (HOXB9) Abd-B homeobox family P17482
Homeobox protein Hox-C8 (HOXC8) Antp homeobox family P31273
Homeobox protein Hox-A1 (HOXA1) Antp homeobox family P49639
Transcription factor AP-2-delta (TFAP2D) AP-2 family Q7Z6R9
RB-associated KRAB zinc finger protein (RBAK) Krueppel C2H2-type zinc-finger protein family Q9NYW8
Transcriptional repressor RHIT (ZNF205) Krueppel C2H2-type zinc-finger protein family O95201
Zinc finger imprinted 2 (ZIM2) Krueppel C2H2-type zinc-finger protein family Q9NZV7
Zinc finger protein 134 (ZNF134) Krueppel C2H2-type zinc-finger protein family P52741
Zinc finger protein 417 (ZNF417) Krueppel C2H2-type zinc-finger protein family Q8TAU3
Zinc finger protein 497 (ZNF497) Krueppel C2H2-type zinc-finger protein family Q6ZNH5
Zinc finger protein 575 (ZNF575) Krueppel C2H2-type zinc-finger protein family Q86XF7
Zinc finger protein 587 (ZNF587) Krueppel C2H2-type zinc-finger protein family Q96SQ5
Zinc finger protein 648 (ZNF648) Krueppel C2H2-type zinc-finger protein family Q5T619
Zinc finger protein 837 (ZNF837) Krueppel C2H2-type zinc-finger protein family Q96EG3
Cone-rod homeobox protein (CRX) Paired homeobox family O43186
Homeobox protein OTX1 (OTX1) Paired homeobox family P32242
PHD finger protein 1 (PHF1) Polycomblike family O43189
AT-rich interactive domain-containing protein 5A (ARID5A) . Q03989
Golgin-45 (BLZF1) . Q9H2G9
Myb-related transcription factor, partner of profilin (MYPOP) . Q86VE0
Proto-oncogene c-Rel (REL) . Q04864
Cytokine and receptor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Tumor necrosis factor ligand superfamily member 6 (FASLG) Tumor necrosis factor family P48023
Other
Click To Hide/Show 35 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Plakophilin-1 (PKP1) Beta-catenin family Q13835
Mammalian ependymin-related protein 1 (EPDR1) Ependymin family Q9UM22
Protein FAM228A (FAM228A) FAM228 family Q86W67
Keratin, type II cytoskeletal 2 oral (KRT76) Intermediate filament family Q01546
Keratin-associated protein 1-3 (KRTAP1-3) KRTAP type 1 family Q8IUG1
Keratin-associated protein 10-5 (KRTAP10-5) KRTAP type 10 family P60370
Keratin-associated protein 10-7 (KRTAP10-7) KRTAP type 10 family P60409
Keratin-associated protein 10-8 (KRTAP10-8) KRTAP type 10 family P60410
Keratin-associated protein 12-2 (KRTAP12-2) KRTAP type 12 family P59991
Keratin-associated protein 12-3 (KRTAP12-3) KRTAP type 12 family P60328
Keratin-associated protein 4-4 (KRTAP4-4) KRTAP type 4 family Q9BYR3
Cytosolic Fe-S cluster assembly factor NUBP2 (NUBP2) Mrp/NBP35 ATP-binding proteins family Q9Y5Y2
Notch homolog 2 N-terminal-like protein C (NOTCH2NLC) NOTCH family P0DPK4
Leupaxin (LPXN) Paxillin family O60711
Keratin-associated protein 11-1 (KRTAP11-1) PMG family Q8IUC1
Keratin-associated protein 13-2 (KRTAP13-2) PMG family Q52LG2
RNA guanine-N7 methyltransferase activating subunit (RAMAC) RAM family Q9BTL3
Shiftless antiviral inhibitor of ribosomal frameshifting protein (SHFL) SHFL family Q9NUL5
Tektin-3 (TEKT3) Tektin family Q9BXF9
Tektin-5 (TEKT5) Tektin family Q96M29
Synaptic plasticity regulator PANTS (C22orf39) UPF0545 family Q6P5X5
Bromo adjacent homology domain-containing 1 protein (BAHD1) . Q8TBE0
BTB/POZ domain-containing protein KCTD9 (KCTD9) . Q7L273
Enkurin domain-containing protein 1 (ENKD1) . Q9H0I2
INO80 complex subunit B (INO80B) . Q9C086
Keratinocyte proline-rich protein (KPRP) . Q5T749
Lamin tail domain-containing protein 2 (LMNTD2) . Q8IXW0
Leucine zipper protein 4 (LUZP4) . Q9P127
SERTA domain-containing protein 2 (SERTAD2) . Q14140
Suppressor of cytokine signaling 7 (SOCS7) . O14512
Sushi domain-containing protein 2 (SUSD2) . Q9UGT4
Uncharacterized protein C11orf87 (C11orf87) . Q6NUJ2
Uncharacterized protein C1orf94 (C1orf94) . Q6P1W5
Vinexin (SORBS3) . O60504
Zinc finger CCHC domain-containing protein 14 (ZCCHC14) . Q8WYQ9

References

1 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
2 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
3 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
4 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761