Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ8V0KG)

DOT Name	Histone H2B type 1-K (H2BC12)
Synonyms	H2B K; HIRA-interacting protein 1
Gene Name	H2BC12
Related Disease	Advanced cancer ( ) Alzheimer disease ( ) Autism ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Childhood acute lymphoblastic leukemia ( ) Epithelial ovarian cancer ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Triple negative breast cancer ( ) Glioblastoma multiforme ( )
UniProt ID	H2B1K_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2CV5 ; 6KE9 ; 6L9H ; 6LE9 ; 6T79 ; 6T7A ; 6T7B ; 6T7C ; 6T7D ; 6V92 ; 6Y5D ; 7BWD ; 7DBP ; 7JZV ; 7PET ; 7PEU ; 7PEV ; 7PEW ; 7PEX ; 7PEY ; 7PEZ ; 7PF0 ; 7PF2 ; 7PF3 ; 7PF4 ; 7PF5 ; 7PF6 ; 7PFA ; 7PFC ; 7PFD ; 7PFE ; 7PFF ; 7PFT ; 7PFU ; 7PFV ; 7PFW ; 7PFX ; 7V90 ; 7V96 ; 7V99 ; 7V9C ; 7V9J ; 7V9K ; 7V9S ; 7VA4 ; 7XCR ; 7XCT ; 7XD1 ; 8GRQ ; 8HQY ; 8HR1 ; 8IEG ; 8IEJ ; 8JHF ; 8JHG
Pfam ID	PF00125
Sequence	MPEPAKSAPAPKKGSKKAVTKAQKKDGKKRKRSRKESYSVYVYKVLKQVHPDTGISSKAM GIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVT KYTSAK
Function	Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.; Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.
KEGG Pathway	Neutrophil extracellular trap formation (hsa04613 ) Alcoholism (hsa05034 ) Viral carcinogenesis (hsa05203 ) Systemic lupus erythematosus (hsa05322 )
Reactome Pathway	Cleavage of the damaged pyrimidine (R-HSA-110329 ) Recognition and association of DNA glycosylase with site containing an affected purine (R-HSA-110330 ) Cleavage of the damaged purine (R-HSA-110331 ) Meiotic synapsis (R-HSA-1221632 ) Packaging Of Telomere Ends (R-HSA-171306 ) Pre-NOTCH Transcription and Translation (R-HSA-1912408 ) Formation of the beta-catenin (R-HSA-201722 ) PRC2 methylates histones and DNA (R-HSA-212300 ) Condensation of Prophase Chromosomes (R-HSA-2299718 ) Oxidative Stress Induced Senescence (R-HSA-2559580 ) Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582 ) DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586 ) HDACs deacetylate histones (R-HSA-3214815 ) HATs acetylate histones (R-HSA-3214847 ) SIRT1 negatively regulates rRNA expression (R-HSA-427359 ) ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression (R-HSA-427389 ) NoRC negatively regulates rRNA expression (R-HSA-427413 ) B-WICH complex positively regulates rRNA expression (R-HSA-5250924 ) DNA methylation (R-HSA-5334118 ) Transcriptional regulation by small RNAs (R-HSA-5578749 ) Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472 ) Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (R-HSA-5625886 ) Ub-specific processing proteases (R-HSA-5689880 ) Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565 ) Nonhomologous End-Joining (NHEJ) (R-HSA-5693571 ) Processing of DNA double-strand break ends (R-HSA-5693607 ) Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279 ) Assembly of the ORC complex at the origin of replication (R-HSA-68616 ) G2/M DNA damage checkpoint (R-HSA-69473 ) RNA Polymerase I Promoter Opening (R-HSA-73728 ) RNA Polymerase I Promoter Escape (R-HSA-73772 ) E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654 ) RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459 ) RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236 ) Estrogen-dependent gene expression (R-HSA-9018519 ) Meiotic recombination (R-HSA-912446 ) HCMV Early Events (R-HSA-9609690 ) HCMV Late Events (R-HSA-9610379 ) Transcriptional regulation of granulopoiesis (R-HSA-9616222 ) Inhibition of DNA recombination at telomere (R-HSA-9670095 ) Defective pyroptosis (R-HSA-9710421 ) Amyloid fiber formation (R-HSA-977225 ) Chromatin modifications during the maternal to zygotic transition (MZT) (R-HSA-9821002 ) Replacement of protamines by nucleosomes in the male pronucleus (R-HSA-9821993 ) Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[1]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[1]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[1]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[6]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[7]
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⏷ Show the Full List of 12 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Histone H2B type 1-K (H2BC12).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histone H2B type 1-K (H2BC12).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone H2B type 1-K (H2BC12).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H2B type 1-K (H2BC12).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone H2B type 1-K (H2BC12).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H2B type 1-K (H2BC12).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H2B type 1-K (H2BC12).	[14]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Histone H2B type 1-K (H2BC12).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Histone H2B type 1-K (H2BC12).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone H2B type 1-K (H2BC12).	[17]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Histone H2B type 1-K (H2BC12).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Histone H2B type 1-K (H2BC12).	[19]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Histone H2B type 1-K (H2BC12).	[20]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Histone H2B type 1-K (H2BC12).	[21]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Histone H2B type 1-K (H2BC12).	[22]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Histone H2B type 1-K (H2BC12).	[23]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Histone H2B type 1-K (H2BC12).	[24]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Histone H2B type 1-K (H2BC12).	[25]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide increases the expression of Histone H2B type 1-K (H2BC12).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histone H2B type 1-K (H2BC12).	[27]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H2B type 1-K (H2BC12).	[28]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Histone H2B type 1-K (H2BC12).	[21]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Histone H2B type 1-K (H2BC12).	[21]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Histone H2B type 1-K (H2BC12).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Histone H2B type 1-K (H2BC12).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Histone H2B type 1-K (H2BC12).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Histone H2B type 1-K (H2BC12).	[33]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone H2B type 1-K (H2BC12).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone H2B type 1-K (H2BC12).	[34]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Histone H2B type 1-K (H2BC12).	[35]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Histone H2B type 1-K (H2BC12).	[36]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Histone H2B type 1-K (H2BC12).	[37]
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⏷ Show the Full List of 32 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Histone H2B type 1-K (H2BC12).	[32]
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