Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU223PA)

• DOT Name: Intracellular hyaluronan-binding protein 4 (HABP4)
• Synonyms: IHABP-4; IHABP4; Hyaluronan-binding protein 4; Ki-1/57 intracellular antigen
• Gene Name: HABP4
• Related Disease: Classic Hodgkin lymphoma
• UniProt ID: HABP4_HUMAN
• Pfam ID: PF04774 ; PF16174
• Sequence:
  MKGALGSPVAAAGAAMQESFGCVVANRFHQLLDDESDPFDILREAERRRQQQLQRKRRDE
  AAAAAGAGPRGGRSPAGASGHRAGAGGRRESQKERKSLPAPVAQRPDSPGGGLQAPGQKR
  TPRRGEQQGWNDSRGPEGMLERAERRSYREYRPYETERQADFTAEKFPDEKPGDRFDRDR
  PLRGRGGPRGGMRGRGRGGPGNRVFDAFDQRGKREFERYGGNDKIAVRTEDNMGGCGVRT
  WGSGKDTSDVEPTAPMEEPTVVEESQGTPEEESPAKVPELEVEEETQVQEMTLDEWKNLQ
  EQTRPKPEFNIRKPESTVPSKAVVIHKSKYRDDMVKDDYEDDSHVFRKPANDITSQLEIN
  FGNLPRPGRGARGGTRGGRGRIRRAENYGPRAEVVMQDVAPNPDDPEDFPALS
• Function: Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation. Acts via its association with EEF2/eEF2 factor at the A-site of the ribosome, promoting ribosome stabilization in an inactive state compatible with storage. Plays a key role in ribosome hibernation in the mature oocyte by promoting ribosome stabilization. Ribosomes, which are produced in large quantities during oogenesis, are stored and translationally repressed in the oocyte and early embryo. Also binds RNA, regulating transcription and pre-mRNA splicing. Binds (via C-terminus) to poly(U) RNA. Seems to play a role in PML-nuclear bodies formation. Negatively regulates DNA-binding activity of the transcription factor MEF2C in myocardial cells in response to mechanical stress.
• Tissue Specificity: Highly expressed in brain, heart, and kidney, and moderately expressed in skeletal muscle. Also expressed in a variety of tumor cell lines and in activated but not resting leukocytes.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[1]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Intracellular hyaluronan-binding protein 4 (HABP4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Intracellular hyaluronan-binding protein 4 (HABP4).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Intracellular hyaluronan-binding protein 4 (HABP4).	[9]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Intracellular hyaluronan-binding protein 4 (HABP4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Intracellular hyaluronan-binding protein 4 (HABP4).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Intracellular hyaluronan-binding protein 4 (HABP4).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Intracellular hyaluronan-binding protein 4 (HABP4).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Intracellular hyaluronan-binding protein 4 (HABP4).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Intracellular hyaluronan-binding protein 4 (HABP4).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Intracellular hyaluronan-binding protein 4 (HABP4).	[11]

References

• [1] Human Regulatory Protein Ki-1/57 Is a Target of SUMOylation and Affects PML Nuclear Body Formation.J Proteome Res. 2017 Sep 1;16(9):3147-3157. doi: 10.1021/acs.jproteome.7b00001. Epub 2017 Jul 31.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.