Details of the Target

General Information of Target

Target ID LDTP07452
Target Name Methylcytosine dioxygenase TET2 (TET2)
Gene Name TET2
Gene ID 54790
Synonyms
KIAA1546; Methylcytosine dioxygenase TET2; EC 1.14.11.80
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MEQDRTNHVEGNRLSPFLIPSPPICQTEPLATKLQNGSPLPERAHPEVNGDTKWHSFKSY
YGIPCMKGSQNSRVSPDFTQESRGYSKCLQNGGIKRTVSEPSLSGLLQIKKLKQDQKANG
ERRNFGVSQERNPGESSQPNVSDLSDKKESVSSVAQENAVKDFTSFSTHNCSGPENPELQ
ILNEQEGKSANYHDKNIVLLKNKAVLMPNGATVSASSVEHTHGELLEKTLSQYYPDCVSI
AVQKTTSHINAINSQATNELSCEITHPSHTSGQINSAQTSNSELPPKPAAVVSEACDADD
ADNASKLAAMLNTCSFQKPEQLQQQKSVFEICPSPAENNIQGTTKLASGEEFCSGSSSNL
QAPGGSSERYLKQNEMNGAYFKQSSVFTKDSFSATTTPPPPSQLLLSPPPPLPQVPQLPS
EGKSTLNGGVLEEHHHYPNQSNTTLLREVKIEGKPEAPPSQSPNPSTHVCSPSPMLSERP
QNNCVNRNDIQTAGTMTVPLCSEKTRPMSEHLKHNPPIFGSSGELQDNCQQLMRNKEQEI
LKGRDKEQTRDLVPPTQHYLKPGWIELKAPRFHQAESHLKRNEASLPSILQYQPNLSNQM
TSKQYTGNSNMPGGLPRQAYTQKTTQLEHKSQMYQVEMNQGQSQGTVDQHLQFQKPSHQV
HFSKTDHLPKAHVQSLCGTRFHFQQRADSQTEKLMSPVLKQHLNQQASETEPFSNSHLLQ
HKPHKQAAQTQPSQSSHLPQNQQQQQKLQIKNKEEILQTFPHPQSNNDQQREGSFFGQTK
VEECFHGENQYSKSSEFETHNVQMGLEEVQNINRRNSPYSQTMKSSACKIQVSCSNNTHL
VSENKEQTTHPELFAGNKTQNLHHMQYFPNNVIPKQDLLHRCFQEQEQKSQQASVLQGYK
NRNQDMSGQQAAQLAQQRYLIHNHANVFPVPDQGGSHTQTPPQKDTQKHAALRWHLLQKQ
EQQQTQQPQTESCHSQMHRPIKVEPGCKPHACMHTAPPENKTWKKVTKQENPPASCDNVQ
QKSIIETMEQHLKQFHAKSLFDHKALTLKSQKQVKVEMSGPVTVLTRQTTAAELDSHTPA
LEQQTTSSEKTPTKRTAASVLNNFIESPSKLLDTPIKNLLDTPVKTQYDFPSCRCVEQII
EKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVV
RRSSSEEKLLCLVRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTN
RRCALNEERTCACQGLDPETCGASFSFGCSWSMYYNGCKFARSKIPRKFKLLGDDPKEEE
KLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFSGVTACLDFCAH
AHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKR
SGAIQVLSSFRRKVRMLAEPVKTCRQRKLEAKKAAAEKLSSLENSSNKNEKEKSAPSRTK
QTENASQAKQLAELLRLSGPVMQQSQQPQPLQKQPPQPQQQQRPQQQQPHHPQTESVNSY
SASGSTNPYMRRPNPVSPYPNSSHTSDIYGSTSPMNFYSTSSQAAGSYLNSSNPMNPYPG
LLNQNTQYPSYQCNGNLSVDNCSPYLGSYSPQSQPMDLYRYPSQDPLSKLSLPPIHTLYQ
PRFGNSQSFTSKYLGYGNQNMQGDGFSSCTIRPNVHHVGKLPPYPTHEMDGHFMGATSRL
PPNLSNPNMDYKNGEHHSPSHIIHNYSAAPGMFNSSLHALHLQNKENDMLSHTANGLSKM
LPALNHDRTACVQGGLHKLSDANGQEKQPLALVQGVASGAEDNDEVWSDSEQSFLDPDIG
GVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAK
MAEKAREKEEECEKYGPDYVPQKSHGKKVKREPAEPHETSEPTYLRFIKSLAERTMSVTT
DSTVTTSPYAFTRVTGPYNRYI
Target Bioclass
Enzyme
Family
TET family
Subcellular location
Nucleus
Function
Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT.
Uniprot ID
Q6N021
Ensemble ID
ENST00000265149.9
HGNC ID
HGNC:25941
ChEMBL ID
CHEMBL4523344

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A2058 Substitution: p.P139L .
AGS SNV: p.P1316L DBIA    Probe Info 
CCK81 SNV: p.M695V; p.A1810T .
COLO829 SNV: p.A1341V .
DU145 Insertion: p.T229NfsTer25 .
HS936T SNV: p.P16L .
HT SNV: p.H658P .
HT115 SNV: p.K1947N .
JHH6 SNV: p.P656R .
JURKAT SNV: p.Q1526R .
KO52 Insertion: p.Y1560Ter .
KYM1 SNV: p.V386L .
LS123 SNV: p.H1868N .
MDAMB453 SNV: p.R881G .
MFE319 SNV: p.V1812L .
NALM6 SNV: p.R1261H DBIA    Probe Info 
NCIH2172 SNV: p.N483D .
OCIAML5 SNV: p.S825Ter .
OVKATE SNV: p.G1754S DBIA    Probe Info 
PC9 Insertion: p.P1655HfsTer6
SNV: p.P1655R		 .
RKO SNV: p.G678D; p.D1981G .
SKMEL5 SNV: p.S477F .
TCCSUP SNV: p.L694R .
U2OS SNV: p.P465L .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info  		K568(10.00)  LDD0277  [1]
DBIA
 Probe Info  		C1811(1.30)  LDD3323  [2]
IA-alkyne
 Probe Info  		C882(8.07)  LDD1706  [3]
NAIA_5
 Probe Info  		C882(0.00); C1811(0.00)  LDD2224  [4]
IPM
 Probe Info  		N.A.  LDD2156  [5]
YN-1
 Probe Info  		N.A.  LDD0447  [6]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0215  AC10 HEK-293T C1263(1.20); C784(1.07)  LDD1508  [7]
 LDCM0277  AC18 HEK-293T C1263(0.99); C784(0.91)  LDD1516  [7]
 LDCM0279  AC2 HEK-293T C1263(1.07); C784(1.12)  LDD1518  [7]
 LDCM0284  AC24 HEK-293T C882(1.00)  LDD1523  [7]
 LDCM0286  AC26 HEK-293T C1263(0.82); C784(1.13)  LDD1525  [7]
 LDCM0293  AC32 HEK-293T C882(0.96)  LDD1532  [7]
 LDCM0295  AC34 HEK-293T C1263(1.61); C784(1.12)  LDD1534  [7]
 LDCM0302  AC40 HEK-293T C882(1.02)  LDD1541  [7]
 LDCM0304  AC42 HEK-293T C1263(1.43); C784(1.26)  LDD1543  [7]
 LDCM0310  AC48 HEK-293T C882(1.09)  LDD1549  [7]
 LDCM0313  AC50 HEK-293T C1263(1.30); C784(1.13)  LDD1552  [7]
 LDCM0319  AC56 HEK-293T C882(1.09)  LDD1558  [7]
 LDCM0321  AC58 HEK-293T C1263(1.11); C784(1.04)  LDD1560  [7]
 LDCM0328  AC64 HEK-293T C882(1.05)  LDD1567  [7]
 LDCM0345  AC8 HEK-293T C882(1.09)  LDD1569  [7]
 LDCM0275  AKOS034007705 HEK-293T C882(1.04)  LDD1514  [7]
 LDCM0632  CL-Sc Hep-G2 C1811(0.94)  LDD2227  [4]
 LDCM0371  CL102 HEK-293T C1263(1.31)  LDD1575  [7]
 LDCM0375  CL106 HEK-293T C1263(1.22)  LDD1579  [7]
 LDCM0380  CL110 HEK-293T C1263(1.11)  LDD1584  [7]
 LDCM0384  CL114 HEK-293T C1263(0.99)  LDD1588  [7]
 LDCM0388  CL118 HEK-293T C1263(1.53)  LDD1592  [7]
 LDCM0390  CL12 HEK-293T C882(1.17)  LDD1594  [7]
 LDCM0393  CL122 HEK-293T C1263(1.28)  LDD1597  [7]
 LDCM0397  CL126 HEK-293T C1263(1.09)  LDD1601  [7]
 LDCM0401  CL14 HEK-293T C1263(1.56)  LDD1605  [7]
 LDCM0405  CL18 HEK-293T C1263(1.11); C784(1.00)  LDD1609  [7]
 LDCM0407  CL2 HEK-293T C1263(1.00)  LDD1611  [7]
 LDCM0412  CL24 HEK-293T C882(1.12)  LDD1616  [7]
 LDCM0414  CL26 HEK-293T C1263(1.24)  LDD1618  [7]
 LDCM0419  CL30 HEK-293T C1263(1.45); C784(0.78)  LDD1623  [7]
 LDCM0425  CL36 HEK-293T C882(1.13)  LDD1629  [7]
 LDCM0432  CL42 HEK-293T C1263(1.19); C784(1.13)  LDD1636  [7]
 LDCM0438  CL48 HEK-293T C882(1.16)  LDD1642  [7]
 LDCM0441  CL50 HEK-293T C1263(1.15)  LDD1645  [7]
 LDCM0445  CL54 HEK-293T C1263(1.33); C784(1.10)  LDD1648  [7]
 LDCM0451  CL6 HEK-293T C1263(1.25); C784(0.87)  LDD1654  [7]
 LDCM0452  CL60 HEK-293T C882(1.28)  LDD1655  [7]
 LDCM0454  CL62 HEK-293T C1263(1.36)  LDD1657  [7]
 LDCM0458  CL66 HEK-293T C1263(0.90); C784(0.98)  LDD1661  [7]
 LDCM0465  CL72 HEK-293T C882(1.33)  LDD1668  [7]
 LDCM0467  CL74 HEK-293T C1263(1.02)  LDD1670  [7]
 LDCM0471  CL78 HEK-293T C1263(1.19); C784(1.18)  LDD1674  [7]
 LDCM0478  CL84 HEK-293T C882(1.05)  LDD1681  [7]
 LDCM0480  CL86 HEK-293T C1263(1.05)  LDD1683  [7]
 LDCM0485  CL90 HEK-293T C1263(1.81); C784(1.19)  LDD1688  [7]
 LDCM0491  CL96 HEK-293T C882(1.01)  LDD1694  [7]
 LDCM0493  CL98 HEK-293T C1263(1.46)  LDD1696  [7]
 LDCM0427  Fragment51 HEK-293T C1263(1.39)  LDD1631  [7]
 LDCM0022  KB02 HEK-293T C1016(1.26)  LDD1492  [7]
 LDCM0023  KB03 HEK-293T C1016(0.97)  LDD1497  [7]
 LDCM0024  KB05 SKMEL24 C1811(1.30)  LDD3323  [2]

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
UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit (OGT) Glycosyltransferase 41 family O15294
Fibroblast growth factor receptor 3 (FGFR3) Tyr protein kinase family P22607
Protein PML (PML) . P29590
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Wilms tumor protein (WT1) EGR C2H2-type zinc-finger protein family P19544
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Gelsolin (GSN) Villin/gelsolin family P06396

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
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 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.
4 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
5 Benchmarking Cleavable Biotin Tags for Peptide-Centric Chemoproteomics. J Proteome Res. 2022 May 6;21(5):1349-1358. doi: 10.1021/acs.jproteome.2c00174. Epub 2022 Apr 25.
Mass spectrometry data entry: PXD031019
6 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
7 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402