General Information of Target

Target ID LDTP10599
Target Name YTH domain-containing protein 1 (YTHDC1)
Gene Name YTHDC1
Gene ID 91746
Synonyms
KIAA1966; YT521; YTH domain-containing protein 1; Splicing factor YT521; YT521-B
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEALLEGIQNRGHGGGFLTSCEAELQELMKQIDIMVAHKKSEWEGRTHALETCLKIREQE
LKSLRSQLDVTHKEVGMLHQQVEEHEKIKQEMTMEYKQELKKLHEELCILKRSYEKLQKK
QMREFRGNTKNHREDRSEIERLTAKIEEFRQKSLDWEKQRLIYQQQVSSLEAQRKALAEQ
SEIIQAQLVNRKQKLESVELSSQSEIQHLSSKLERANDTICANELEIERLTMRVNDLVGT
SMTVLQEQQQKEEKLRESEKLLEALQEEKRELKAALQSQENLIHEARIQKEKLQEKVKAT
NTQHAVEAIRPREESLAEKKYTSQGQGDLDSVLSQLNFTHTSEDLLQAEVTCLEGSLESV
SATCKQLSQELMEKYEELKRMEAHNNEYKAEIKKLKEQILQGEQSYSSALEGMKMEISHL
TQELHQRDITIASTKGSSSDMEKRLRAEMQKAEDKAVEHKEILDQLESLKLENRHLSEMV
MKLELGLHEAKEISLADLQENYIEALNKLVSENQQLQKDLMNTKSQLEISTQMCKKQNDR
IFKPTHSRTTEFKNTEFKPTHGQHRHDGIKTEHYKTDLHSPRGQASDSINPMSRVLSPLS
PQISPCSSTRSLTSYSLCKTHSLPSALDTNEANFSDTMSESMNDQEEFISSCSLPVSPLG
SIATRFLEEEELRSHHILERLDAHIEELKRESEKTVRQFTALK
Target Bioclass
Other
Subcellular location
Nucleus
Function
Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability. Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10. Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing. In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing. May also regulate alternative splice site selection. Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export. Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs. Also recognizes and binds m6A on other RNA molecules. Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist. Also recognizes and binds m6A-containing single-stranded DNA. Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing.
Uniprot ID
Q96MU7
Ensemble ID
ENST00000344157.9
HGNC ID
HGNC:30626
ChEMBL ID
CHEMBL5169187

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
AN3CA SNV: p.A459T DBIA    Probe Info 
COLO792 SNV: p.R341Ter .
DU145 Deletion: p.K43RfsTer32 .
G361 Substitution: p.P567L .
GB2 SNV: p.K408E .
HCC1954 Deletion: p.E247_E249del .
HUH1 SNV: p.N363Y .
JVM3 Deletion: p.L491VfsTer5 .
LN229 SNV: p.E234K .
MCC26 Substitution: p.S122F .
OV90 SNV: p.R162C .
PEO1 SNV: p.E240Ter .
TE4 SNV: p.D272V .
TOV21G SNV: p.G11V .

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
STPyne
 Probe Info 
K347(6.25); K349(6.25); K361(0.60); K374(5.88)  LDD0277  [1]
DBIA
 Probe Info 
C449(6.52)  LDD3409  [2]
BTD
 Probe Info 
C134(2.46)  LDD2116  [3]
IA-alkyne
 Probe Info 
N.A.  LDD0162  [4]
NAIA_5
 Probe Info 
C449(0.00); C713(0.00)  LDD2224  [5]
IPM
 Probe Info 
C713(0.00); C134(0.00)  LDD0147  [6]
SF
 Probe Info 
Y95(0.00); Y100(0.00)  LDD0028  [7]
Phosphinate-6
 Probe Info 
N.A.  LDD0018  [8]
Acrolein
 Probe Info 
N.A.  LDD0217  [9]
Crotonaldehyde
 Probe Info 
N.A.  LDD0219  [9]
Methacrolein
 Probe Info 
N.A.  LDD0218  [9]
PAL-AfBPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FFF probe2
 Probe Info 
20.00  LDD0463  [10]
FFF probe3
 Probe Info 
6.40  LDD0464  [10]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0215  AC10 PaTu 8988t C484(0.68); C489(0.68)  LDD1094  [11]
 LDCM0226  AC11 PaTu 8988t C484(0.68); C489(0.68)  LDD1105  [11]
 LDCM0237  AC12 PaTu 8988t C484(0.84); C489(0.84)  LDD1116  [11]
 LDCM0259  AC14 PaTu 8988t C484(0.91); C489(0.91)  LDD1138  [11]
 LDCM0270  AC15 PaTu 8988t C484(0.65); C489(0.65)  LDD1149  [11]
 LDCM0277  AC18 HEK-293T C489(1.12)  LDD1516  [12]
 LDCM0278  AC19 HEK-293T C484(1.03)  LDD1517  [12]
 LDCM0279  AC2 HEK-293T C489(1.01)  LDD1518  [12]
 LDCM0280  AC20 HEK-293T C484(0.99)  LDD1519  [12]
 LDCM0282  AC22 HEK-293T C484(1.05)  LDD1521  [12]
 LDCM0285  AC25 PaTu 8988t C484(0.82); C489(0.82)  LDD1164  [11]
 LDCM0286  AC26 PaTu 8988t C484(1.23); C489(1.23)  LDD1165  [11]
 LDCM0287  AC27 PaTu 8988t C484(0.89); C489(0.89)  LDD1166  [11]
 LDCM0288  AC28 PaTu 8988t C484(0.84); C489(0.84)  LDD1167  [11]
 LDCM0289  AC29 PaTu 8988t C484(1.00); C489(1.00)  LDD1168  [11]
 LDCM0290  AC3 HEK-293T C484(0.96)  LDD1529  [12]
 LDCM0291  AC30 PaTu 8988t C484(0.89); C489(0.89)  LDD1170  [11]
 LDCM0292  AC31 PaTu 8988t C484(1.03); C489(1.03)  LDD1171  [11]
 LDCM0293  AC32 PaTu 8988t C484(1.21); C489(1.21)  LDD1172  [11]
 LDCM0294  AC33 PaTu 8988t C484(0.94); C489(0.94)  LDD1173  [11]
 LDCM0295  AC34 PaTu 8988t C484(0.98); C489(0.98)  LDD1174  [11]
 LDCM0296  AC35 PaTu 8988t C484(0.89); C489(0.89)  LDD1175  [11]
 LDCM0297  AC36 PaTu 8988t C484(0.80); C489(0.80)  LDD1176  [11]
 LDCM0298  AC37 PaTu 8988t C484(0.76); C489(0.76)  LDD1177  [11]
 LDCM0299  AC38 PaTu 8988t C484(0.94); C489(0.94)  LDD1178  [11]
 LDCM0300  AC39 PaTu 8988t C484(1.00); C489(1.00)  LDD1179  [11]
 LDCM0301  AC4 HEK-293T C484(0.91)  LDD1540  [12]
 LDCM0302  AC40 PaTu 8988t C484(0.96); C489(0.96)  LDD1181  [11]
 LDCM0303  AC41 PaTu 8988t C484(1.01); C489(1.01)  LDD1182  [11]
 LDCM0304  AC42 PaTu 8988t C484(1.03); C489(1.03)  LDD1183  [11]
 LDCM0305  AC43 PaTu 8988t C484(0.81); C489(0.81)  LDD1184  [11]
 LDCM0306  AC44 PaTu 8988t C484(0.96); C489(0.96)  LDD1185  [11]
 LDCM0307  AC45 PaTu 8988t C484(1.00); C489(1.00)  LDD1186  [11]
 LDCM0308  AC46 PaTu 8988t C484(1.20); C489(1.20)  LDD1187  [11]
 LDCM0309  AC47 PaTu 8988t C484(1.08); C489(1.08)  LDD1188  [11]
 LDCM0310  AC48 PaTu 8988t C484(1.01); C489(1.01)  LDD1189  [11]
 LDCM0311  AC49 PaTu 8988t C484(1.29); C489(1.29)  LDD1190  [11]
 LDCM0313  AC50 PaTu 8988t C484(1.30); C489(1.30)  LDD1192  [11]
 LDCM0314  AC51 PaTu 8988t C484(1.43); C489(1.43)  LDD1193  [11]
 LDCM0315  AC52 PaTu 8988t C484(1.30); C489(1.30)  LDD1194  [11]
 LDCM0316  AC53 PaTu 8988t C484(1.36); C489(1.36)  LDD1195  [11]
 LDCM0317  AC54 PaTu 8988t C484(1.40); C489(1.40)  LDD1196  [11]
 LDCM0318  AC55 PaTu 8988t C484(1.17); C489(1.17)  LDD1197  [11]
 LDCM0319  AC56 PaTu 8988t C484(1.69); C489(1.69)  LDD1198  [11]
 LDCM0321  AC58 HEK-293T C489(1.03)  LDD1560  [12]
 LDCM0322  AC59 HEK-293T C484(0.92)  LDD1561  [12]
 LDCM0323  AC6 PaTu 8988t C484(0.83); C489(0.83)  LDD1202  [11]
 LDCM0324  AC60 HEK-293T C484(0.93)  LDD1563  [12]
 LDCM0326  AC62 HEK-293T C484(1.06)  LDD1565  [12]
 LDCM0334  AC7 PaTu 8988t C484(1.03); C489(1.03)  LDD1213  [11]
 LDCM0345  AC8 PaTu 8988t C484(0.76); C489(0.76)  LDD1224  [11]
 LDCM0248  AKOS034007472 PaTu 8988t C484(1.10); C489(1.10)  LDD1127  [11]
 LDCM0356  AKOS034007680 PaTu 8988t C484(0.76); C489(0.76)  LDD1235  [11]
 LDCM0275  AKOS034007705 PaTu 8988t C484(0.76); C489(0.76)  LDD1154  [11]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [9]
 LDCM0368  CL10 HEK-293T C484(0.99)  LDD1572  [12]
 LDCM0370  CL101 PaTu 8988t C484(0.76); C489(0.76)  LDD1249  [11]
 LDCM0371  CL102 PaTu 8988t C484(0.66); C489(0.66)  LDD1250  [11]
 LDCM0372  CL103 PaTu 8988t C484(0.95); C489(0.95)  LDD1251  [11]
 LDCM0373  CL104 PaTu 8988t C484(0.95); C489(0.95)  LDD1252  [11]
 LDCM0382  CL112 PaTu 8988t C484(0.90); C489(0.90)  LDD1261  [11]
 LDCM0383  CL113 PaTu 8988t C484(0.86); C489(0.86)  LDD1262  [11]
 LDCM0384  CL114 PaTu 8988t C484(1.03); C489(1.03)  LDD1263  [11]
 LDCM0385  CL115 PaTu 8988t C484(1.12); C489(1.12)  LDD1264  [11]
 LDCM0386  CL116 PaTu 8988t C484(1.05); C489(1.05)  LDD1265  [11]
 LDCM0387  CL117 PaTu 8988t C484(0.91); C489(0.91)  LDD1266  [11]
 LDCM0388  CL118 PaTu 8988t C484(1.38); C489(1.38)  LDD1267  [11]
 LDCM0389  CL119 PaTu 8988t C484(1.02); C489(1.02)  LDD1268  [11]
 LDCM0391  CL120 PaTu 8988t C484(0.91); C489(0.91)  LDD1270  [11]
 LDCM0392  CL121 PaTu 8988t C484(1.05); C489(1.05)  LDD1271  [11]
 LDCM0393  CL122 PaTu 8988t C484(2.36); C489(2.36)  LDD1272  [11]
 LDCM0394  CL123 PaTu 8988t C484(1.18); C489(1.18)  LDD1273  [11]
 LDCM0395  CL124 PaTu 8988t C484(1.19); C489(1.19)  LDD1274  [11]
 LDCM0405  CL18 HEK-293T C489(1.15)  LDD1609  [12]
 LDCM0406  CL19 HEK-293T C484(1.00)  LDD1610  [12]
 LDCM0408  CL20 HEK-293T C484(1.02)  LDD1612  [12]
 LDCM0410  CL22 HEK-293T C484(1.19)  LDD1614  [12]
 LDCM0419  CL30 HEK-293T C489(1.21)  LDD1623  [12]
 LDCM0420  CL31 HEK-293T C484(0.82)  LDD1624  [12]
 LDCM0421  CL32 HEK-293T C484(0.96)  LDD1625  [12]
 LDCM0423  CL34 HEK-293T C484(1.07)  LDD1627  [12]
 LDCM0432  CL42 HEK-293T C489(1.10)  LDD1636  [12]
 LDCM0433  CL43 HEK-293T C484(0.93)  LDD1637  [12]
 LDCM0434  CL44 HEK-293T C484(1.08)  LDD1638  [12]
 LDCM0436  CL46 HEK-293T C484(1.09)  LDD1640  [12]
 LDCM0445  CL54 HEK-293T C489(1.12)  LDD1648  [12]
 LDCM0446  CL55 HEK-293T C484(1.10)  LDD1649  [12]
 LDCM0447  CL56 HEK-293T C484(0.96)  LDD1650  [12]
 LDCM0449  CL58 HEK-293T C484(1.04)  LDD1652  [12]
 LDCM0451  CL6 HEK-293T C489(1.28)  LDD1654  [12]
 LDCM0453  CL61 PaTu 8988t C484(1.02); C489(1.02)  LDD1332  [11]
 LDCM0454  CL62 PaTu 8988t C484(1.06); C489(1.06)  LDD1333  [11]
 LDCM0455  CL63 PaTu 8988t C484(1.20); C489(1.20)  LDD1334  [11]
 LDCM0456  CL64 PaTu 8988t C484(0.94); C489(0.94)  LDD1335  [11]
 LDCM0457  CL65 PaTu 8988t C484(0.82); C489(0.82)  LDD1336  [11]
 LDCM0458  CL66 PaTu 8988t C484(0.93); C489(0.93)  LDD1337  [11]
 LDCM0459  CL67 PaTu 8988t C484(1.00); C489(1.00)  LDD1338  [11]
 LDCM0460  CL68 PaTu 8988t C484(1.11); C489(1.11)  LDD1339  [11]
 LDCM0461  CL69 PaTu 8988t C484(1.00); C489(1.00)  LDD1340  [11]
 LDCM0462  CL7 HEK-293T C484(0.98)  LDD1665  [12]
 LDCM0463  CL70 PaTu 8988t C484(0.95); C489(0.95)  LDD1342  [11]
 LDCM0464  CL71 PaTu 8988t C484(1.17); C489(1.17)  LDD1343  [11]
 LDCM0465  CL72 PaTu 8988t C484(1.23); C489(1.23)  LDD1344  [11]
 LDCM0466  CL73 PaTu 8988t C484(1.14); C489(1.14)  LDD1345  [11]
 LDCM0467  CL74 PaTu 8988t C484(1.36); C489(1.36)  LDD1346  [11]
 LDCM0471  CL78 HEK-293T C489(1.02)  LDD1674  [12]
 LDCM0472  CL79 HEK-293T C484(0.92)  LDD1675  [12]
 LDCM0473  CL8 HEK-293T C484(1.68)  LDD1676  [12]
 LDCM0474  CL80 HEK-293T C484(0.90)  LDD1677  [12]
 LDCM0476  CL82 HEK-293T C484(1.00)  LDD1679  [12]
 LDCM0485  CL90 HEK-293T C489(0.80)  LDD1688  [12]
 LDCM0486  CL91 HEK-293T C484(0.86)  LDD1689  [12]
 LDCM0487  CL92 HEK-293T C484(1.00)  LDD1690  [12]
 LDCM0489  CL94 HEK-293T C484(1.09)  LDD1692  [12]
 LDCM0468  Fragment33 PaTu 8988t C484(1.05); C489(1.05)  LDD1347  [11]
 LDCM0107  IAA HeLa N.A.  LDD0221  [9]
 LDCM0022  KB02 A673 C449(3.26)  LDD2261  [2]
 LDCM0023  KB03 A673 C449(10.11)  LDD2678  [2]
 LDCM0024  KB05 RL95-2 C449(6.52)  LDD3409  [2]
 LDCM0109  NEM HeLa N.A.  LDD0227  [9]
 LDCM0523  Nucleophilic fragment 24b MDA-MB-231 C134(2.46)  LDD2116  [3]
 LDCM0525  Nucleophilic fragment 25b MDA-MB-231 C713(2.01)  LDD2118  [3]
 LDCM0527  Nucleophilic fragment 26b MDA-MB-231 C713(0.94)  LDD2120  [3]
 LDCM0529  Nucleophilic fragment 27b MDA-MB-231 C134(15.40)  LDD2122  [3]
 LDCM0531  Nucleophilic fragment 28b MDA-MB-231 C713(2.48)  LDD2124  [3]
 LDCM0555  Nucleophilic fragment 7b MDA-MB-231 C134(10.89)  LDD2149  [3]

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
SRSF protein kinase 1 (SRPK1) CMGC Ser/Thr protein kinase family Q96SB4
SRSF protein kinase 2 (SRPK2) CMGC Ser/Thr protein kinase family P78362
Dual specificity protein kinase CLK2 (CLK2) CMGC Ser/Thr protein kinase family P49760
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
RNA-binding protein with serine-rich domain 1 (RNPS1) Splicing factor SR family Q15287
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
PHD finger protein 19 (PHF19) Polycomblike family Q5T6S3
Other
Click To Hide/Show 10 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Segment polarity protein dishevelled homolog DVL-3 (DVL3) DSH family Q92997
KH domain-containing, RNA-binding, signal transduction-associated protein 2 (KHDRBS2) KHDRBS family Q5VWX1
KH domain-containing, RNA-binding, signal transduction-associated protein 3 (KHDRBS3) KHDRBS family O75525
Keratin-associated protein 10-6 (KRTAP10-6) KRTAP type 10 family P60371
Transformer-2 protein homolog beta (TRA2B) Splicing factor SR family P62995
Heterogeneous nuclear ribonucleoprotein K (HNRNPK) . P61978
PRKCA-binding protein (PICK1) . Q9NRD5
RNA-binding motif protein, Y chromosome, family 1 member F/J (RBMY1F; RBMY1J) . Q15415
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28) . O15084
Syntenin-2 (SDCBP2) . Q9H190

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 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
4 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
5 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
6 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
7 Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows. bioRxiv [Preprint]. 2023 Feb 18:2023.02.17.529022. doi: 10.1101/2023.02.17.529022.
Mass spectrometry data entry: PXD039931
8 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
9 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.
10 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
11 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
12 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