General Information of Target

Target ID LDTP11466
Target Name YTH domain-containing family protein 1 (YTHDF1)
Gene Name YTHDF1
Gene ID 54915
Synonyms
C20orf21; YTH domain-containing family protein 1; DF1; Dermatomyositis associated with cancer putative autoantigen 1; DACA-1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MASKILLNVQEEVTCPICLELLTEPLSLDCGHSLCRACITVSNKEAVTSMGGKSSCPVCG
ISYSFEHLQANQHLANIVERLKEVKLSPDNGKKRDLCDHHGEKLLLFCKEDRKVICWLCE
RSQEHRGHHTVLTEEVFKECQEKLQAVLKRLKKEEEEAEKLEADIREEKTSWKYQVQTER
QRIQTEFDQLRSILNNEEQRELQRLEEEEKKTLDKFAEAEDELVQQKQLVRELISDVECR
SQWSTMELLQDMSGIMKWSEIWRLKKPKMVSKKLKTVFHAPDLSRMLQMFRELTAVRCYW
VDVTLNSVNLNLNLVLSEDQRQVISVPIWPFQCYNYGVLGSQYFSSGKHYWEVDVSKKTA
WILGVYCRTYSRHMKYVVRRCANRQNLYTKYRPLFGYWVIGLQNKCKYGVFEESLSSDPE
VLTLSMAVPPCRVGVFLDYEAGIVSFFNVTSHGSLIYKFSKCCFSQPVYPYFNPWNCPAP
MTLCPPSS
Target Bioclass
Other
Family
YTHDF family, YTHDF1 subfamily
Subcellular location
Cytoplasm
Function
Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, and regulates their stability. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing. Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex. The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) shares m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation. Required to facilitate learning and memory formation in the hippocampus by binding to m6A-containing neuronal mRNAs. Acts as a regulator of axon guidance by binding to m6A-containing ROBO3 transcripts. Acts as a negative regulator of antigen cross-presentation in myeloid dendritic cells. In the context of tumorigenesis, negative regulation of antigen cross-presentation limits the anti-tumor response by reducing efficiency of tumor-antigen cross-presentation. Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation. The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules.
Uniprot ID
Q9BYJ9
Ensemble ID
ENST00000370339.8
HGNC ID
HGNC:15867
ChEMBL ID
CHEMBL5169192

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HCT15 SNV: p.H538Q .
HT115 SNV: p.I115T .
LU65 SNV: p.G133R .
SG231 SNV: p.M269I .
SKMEL2 SNV: p.M51T .
TE11 SNV: p.K380E .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 7 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info 
15.00  LDD0402  [1]
STPyne
 Probe Info 
K240(1.15); K372(8.66); K521(9.09)  LDD0277  [2]
IPM
 Probe Info 
N.A.  LDD0241  [3]
BTD
 Probe Info 
C412(0.97)  LDD2109  [4]
HPAP
 Probe Info 
3.51  LDD0063  [5]
ATP probe
 Probe Info 
N.A.  LDD0199  [6]
Lodoacetamide azide
 Probe Info 
N.A.  LDD0037  [7]
PAL-AfBPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C191
 Probe Info 
9.99  LDD1868  [8]
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
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C412(0.97)  LDD2109  [4]
 LDCM0526  Nucleophilic fragment 26a MDA-MB-231 C412(1.77)  LDD2119  [4]
 LDCM0536  Nucleophilic fragment 31 MDA-MB-231 C412(1.69)  LDD2129  [4]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C412(1.76)  LDD2136  [4]
 LDCM0552  Nucleophilic fragment 6a MDA-MB-231 C412(1.61)  LDD2146  [4]
 LDCM0014  Panhematin K562 3.51  LDD0063  [5]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) HEY family Q9Y5J3
Transcription factor
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Basic leucine zipper transcriptional factor ATF-like 2 (BATF2) BZIP family Q8N1L9
Homeobox protein MSX-2 (MSX2) Msh homeobox family P35548
Other
Click To Hide/Show 8 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Keratin-associated protein 7-1 (KRTAP7-1) KRTAP type 7 family Q8IUC3
Keratin-associated protein 8-1 (KRTAP8-1) KRTAP type 8 family Q8IUC2
Protein Mis18-beta (OIP5) Mis18 family O43482
Keratin-associated protein 26-1 (KRTAP26-1) PMG family Q6PEX3
Vacuolar protein sorting-associated protein 37C (VPS37C) VPS37 family A5D8V6
Melanoma-associated antigen D1 (MAGED1) . Q9Y5V3
Proline-rich protein 32 (PRR32) . B1ATL7
Uncharacterized protein C6orf15 (C6orf15) . Q6UXA7

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 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
3 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
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
5 A Chemical Proteomic Map of Heme-Protein Interactions. J Am Chem Soc. 2022 Aug 24;144(33):15013-15019. doi: 10.1021/jacs.2c06104. Epub 2022 Aug 12.
Mass spectrometry data entry: PXD034651
6 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
7 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
8 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
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.