General Information of Target

Target ID LDTP08274
Target Name THO complex subunit 4 (ALYREF)
Gene Name ALYREF
Gene ID 10189
Synonyms
ALY; BEF; THOC4; THO complex subunit 4; Tho4; Ally of AML-1 and LEF-1; Aly/REF export factor; Transcriptional coactivator Aly/REF; bZIP-enhancing factor BEF
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MADKMDMSLDDIIKLNRSQRGGRGGGRGRGRAGSQGGRGGGAQAAARVNRGGGPIRNRPA
IARGAAGGGGRNRPAPYSRPKQLPDKWQHDLFDSGFGGGAGVETGGKLLVSNLDFGVSDA
DIQELFAEFGTLKKAAVHYDRSGRSLGTADVHFERKADALKAMKQYNGVPLDGRPMNIQL
VTSQIDAQRRPAQSVNRGGMTRNRGAGGFGGGGGTRRGTRGGARGRGRGAGRNSKQQLSA
EELDAQLDAYNARMDTS
Target Bioclass
Transporter and channel
Family
ALYREF family
Subcellular location
Nucleus
Function
Export adapter involved in nuclear export of spliced and unspliced mRNA. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway). Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm. TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production; ALYREF/THOC4 mediates the recruitment of the TREX complex to the intronless viral mRNA. Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC). In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B. Involved in transcription elongation and genome stability. Involved in mRNA export of C5-methylcytosine (m5C)-containing mRNAs: specifically recognizes and binds m5C mRNAs and mediates their nucleo-cytoplasmic shuttling.; Acts as a chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation.
Uniprot ID
Q86V81
HGNC ID
HGNC:19071
ChEMBL ID
CHEMBL4296014

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 19 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
P8
 Probe Info 
10.00  LDD0451  [1]
ILS-1
 Probe Info 
2.04  LDD0415  [2]
C-Sul
 Probe Info 
8.02  LDD0066  [3]
TH211
 Probe Info 
Y77(20.00); Y250(9.65)  LDD0257  [4]
STPyne
 Probe Info 
K134(5.09); K161(10.00); K164(5.60); K235(1.69)  LDD0277  [5]
OPA-S-S-alkyne
 Probe Info 
K235(2.42); K134(4.23)  LDD3494  [6]
Probe 1
 Probe Info 
Y139(22.74); Y166(19.08); Y250(712.40)  LDD3495  [7]
HHS-475
 Probe Info 
Y77(1.41)  LDD0264  [8]
5E-2FA
 Probe Info 
H138(0.00); H89(0.00); H152(0.00)  LDD2235  [9]
ATP probe
 Probe Info 
K235(0.00); K14(0.00); K81(0.00); K86(0.00)  LDD0199  [10]
m-APA
 Probe Info 
H89(0.00); H152(0.00)  LDD2231  [9]
ATP probe
 Probe Info 
N.A.  LDD0035  [11]
NHS
 Probe Info 
N.A.  LDD0010  [12]
SF
 Probe Info 
Y77(0.00); K134(0.00)  LDD0028  [13]
Ox-W18
 Probe Info 
N.A.  LDD2175  [14]
Acrolein
 Probe Info 
N.A.  LDD0217  [15]
Crotonaldehyde
 Probe Info 
H152(0.00); H138(0.00)  LDD0219  [15]
HHS-465
 Probe Info 
N.A.  LDD2240  [16]
HHS-482
 Probe Info 
Y77(0.96)  LDD2239  [17]
PAL-AfBPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FFF probe13
 Probe Info 
7.01  LDD0475  [18]
VE-P
 Probe Info 
N.A.  LDD0396  [19]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0116  HHS-0101 DM93 Y77(1.41)  LDD0264  [8]
 LDCM0117  HHS-0201 DM93 Y77(1.59)  LDD0265  [8]
 LDCM0118  HHS-0301 DM93 Y77(1.17)  LDD0266  [8]
 LDCM0119  HHS-0401 DM93 Y77(1.84)  LDD0267  [8]
 LDCM0120  HHS-0701 DM93 Y77(1.42)  LDD0268  [8]
 LDCM0107  IAA HeLa N.A.  LDD0221  [15]
 LDCM0109  NEM HeLa H152(0.00); H89(0.00)  LDD0223  [15]

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
Spliceosome RNA helicase DDX39B (DDX39B) DEAD box helicase family Q13838
RAC-alpha serine/threonine-protein kinase (AKT1) AGC Ser/Thr protein kinase family P31749
Cyclin-dependent kinase 1 (CDK1) CMGC Ser/Thr protein kinase family P06493
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Nuclear RNA export factor 1 (NXF1) NXF family Q9UBU9
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Chromatin target of PRMT1 protein (CHTOP) . Q9Y3Y2

References

1 Comparison of Different Competitive Proteome Profiling Approaches in Target Identification of Covalent Inhibitors. Chembiochem. 2022 Dec 16;23(24):e202200389. doi: 10.1002/cbic.202200389. Epub 2022 Nov 22.
2 A Chemical Proteomic Analysis of Illudin-Interacting Proteins. Chemistry. 2019 Sep 25;25(54):12644-12651. doi: 10.1002/chem.201902919. Epub 2019 Sep 3.
Mass spectrometry data entry: PXD014175
3 Low-Toxicity Sulfonium-Based Probes for Cysteine-Specific Profiling in Live Cells. Anal Chem. 2022 Mar 15;94(10):4366-4372. doi: 10.1021/acs.analchem.1c05129. Epub 2022 Mar 4.
4 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
5 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
6 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
7 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.
8 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
9 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
10 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.
11 Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer. J Proteome Res. 2018 Jan 5;17(1):63-75. doi: 10.1021/acs.jproteome.7b00329. Epub 2017 Nov 22.
Mass spectrometry data entry: PXD006095 , PXD006096
12 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
13 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
14 Oxidative cyclization reagents reveal tryptophan cation- interactions. Nature. 2024 Mar;627(8004):680-687. doi: 10.1038/s41586-024-07140-6. Epub 2024 Mar 6.
Mass spectrometry data entry: PXD001377 , PXD005252
15 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.
16 Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation. Cell Chem Biol. 2022 Dec 15;29(12):1709-1720.e7. doi: 10.1016/j.chembiol.2022.11.008. Epub 2022 Dec 6.
Mass spectrometry data entry: PXD038010
17 Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. Nat Chem Biol. 2020 Feb;16(2):150-159. doi: 10.1038/s41589-019-0404-5. Epub 2019 Nov 25.
18 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.
19 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.