Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDMCVW7)

• DOT Name: Lysine-specific demethylase 2B (KDM2B)
• Synonyms: EC 1.14.11.27; CXXC-type zinc finger protein 2; F-box and leucine-rich repeat protein 10; F-box protein FBL10; F-box/LRR-repeat protein 10; JmjC domain-containing histone demethylation protein 1B; Jumonji domain-containing EMSY-interactor methyltransferase motif protein; Protein JEMMA; Protein-containing CXXC domain 2; -lysine-36 demethylase 1B
• Gene Name: KDM2B
• Related Disease:
  Acute myelogenous leukaemia
  Adenocarcinoma
  leukaemia
  B-cell lymphoma
  Bladder cancer
  Bone osteosarcoma
  Cardiovascular disease
  Colitis
  Colonic neoplasm
  Dilated cardiomyopathy 1A
  Epithelial ovarian cancer
  Epstein barr virus infection
  Gastric cancer
  Glioma
  Hematologic disease
  Malignant neoplasm
  Malignant peripheral nerve sheath tumor
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Myelodysplastic syndrome
  Nasal polyp
  Neoplasm
  Osteoarthritis
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Schizophrenia
  Stomach cancer
  Synovial sarcoma
  T-cell lymphoma
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colon cancer
  Colon carcinoma
  Squamous cell carcinoma
  Neural tube defect
  Neuroblastoma
  Adult glioblastoma
  Advanced cancer
  Glioblastoma multiforme
  Haematological malignancy
  Intellectual disability
  Leukemia
  Lymphoid leukemia
• UniProt ID: KDM2B_HUMAN
• PDB ID: 4O64; 5JH5; 6BVA
• EC Number: 1.14.11.27
• Pfam ID: PF13621 ; PF12937 ; PF17811 ; PF16866 ; PF02008
• Sequence:
  MAGPQMGGSAEDHPPRKRHAAEKQKKKTVIYTKCFEFESATQRPIDRQRYDENEDLSDVE
  EIVSVRGFSLEEKLRSQLYQGDFVHAMEGKDFNYEYVQREALRVPLIFREKDGLGIKMPD
  PDFTVRDVKLLVGSRRLVDVMDVNTQKGTEMSMSQFVRYYETPEAQRDKLYNVISLEFSH
  TKLEHLVKRPTVVDLVDWVDNMWPQHLKEKQTEATNAIAEMKYPKVKKYCLMSVKGCFTD
  FHIDFGGTSVWYHVFRGGKIFWLIPPTLHNLALYEEWVLSGKQSDIFLGDRVERCQRIEL
  KQGYTFFIPSGWIHAVYTPVDSLVFGGNILHSFNVPMQLRIYEIEDRTRVQPKFRYPFYY
  EMCWYVLERYVYCVTQRSHLTQEYQRESMLIDAPRKPSIDGFSSDSWLEMEEEACDQQPQ
  EEEEKDEEGEGRDRAPKPPTDGSTSPTSTPSEDQEALGKKPKAPALRFLKRTLSNESEES
  VKSTTLAVDYPKTPTGSPATEVSAKWTHLTEFELKGLKALVEKLESLPENKKCVPEGIED
  PQALLEGVKNVLKEHADDDPSLAITGVPVVTWPKKTPKNRAVGRPKGKLGPASAVKLAAN
  RTTAGARRRRTRCRKCEACLRTECGECHFCKDMKKFGGPGRMKQSCIMRQCIAPVLPHTA
  VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECP
  KCNHAGKTGKQKRGPGFKYASNLPGSLLKEQKMNRDNKEGQEPAKRRSECEEAPRRRSDE
  HSKKVPPDGLLRRKSDDVHLRKKRKYEKPQELSGRKRASSLQTSPGSSSHLSPRPPLGSS
  LSPWWRSSLTYFQQQLKPGKEDKLFRKKRRSWKNAEDRMALANKPLRRFKQEPEDELPEA
  PPKTRESDHSRSSSPTAGPSTEGAEGPEEKKKVKMRRKRRLPNKELSRELSKELNHEIQR
  TENSLANENQQPIKSEPESEGEEPKRPPGICERPHRFSKGLNGTPRELRHQLGPSLRSPP
  RVISRPPPSVSPPKCIQMERHVIRPPPISPPPDSLPLDDGAAHVMHREVWMAVFSYLSHQ
  DLCVCMRVCRTWNRWCCDKRLWTRIDLNHCKSITPLMLSGIIRRQPVSLDLSWTNISKKQ
  LSWLINRLPGLRDLVLSGCSWIAVSALCSSSCPLLRTLDVQWVEGLKDAQMRDLLSPPTD
  NRPGQMDNRSKLRNIVELRLAGLDITDASLRLIIRHMPLLSKLHLSYCNHVTDQSINLLT
  AVGTTTRDSLTEINLSDCNKVTDQCLSFFKRCGNICHIDLRYCKQVTKEGCEQFIAEMSV
  SVQFGQVEEKLLQKLS
• Function: Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable).
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway: HDMs demethylate histones (R-HSA-3214842)
• BioCyc Pathway: MetaCyc:HS01631-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Definitive	Biomarker	[2]
leukaemia	DISS7D1V	Definitive	Biomarker	[1]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[6]
Colitis	DISAF7DD	Strong	Biomarker	[7]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[8]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Epstein barr virus infection	DISOO0WT	Strong	Biomarker	[11]
Gastric cancer	DISXGOUK	Strong	Biomarker	[12]
Glioma	DIS5RPEH	Strong	Altered Expression	[13]
Hematologic disease	DIS9XD9A	Strong	Biomarker	[11]
Malignant neoplasm	DISS6SNG	Strong	Biomarker	[11]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Genetic Variation	[14]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[15]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[15]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[16]
Nasal polyp	DISLP3XE	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Osteoarthritis	DIS05URM	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Pancreatic cancer	DISJC981	Strong	Biomarker	[15]
Schizophrenia	DISSRV2N	Strong	Biomarker	[20]
Stomach cancer	DISKIJSX	Strong	Biomarker	[12]
Synovial sarcoma	DISEZJS7	Strong	Biomarker	[21]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[22]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[23]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[24]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[24]
Carcinoma	DISH9F1N	moderate	Altered Expression	[25]
Colon cancer	DISVC52G	moderate	Altered Expression	[26]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[26]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[25]
Neural tube defect	DIS5J95E	Disputed	Altered Expression	[27]
Neuroblastoma	DISVZBI4	Disputed	Altered Expression	[28]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[29]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[30]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[29]
Haematological malignancy	DISCDP7W	Limited	Biomarker	[31]
Intellectual disability	DISMBNXP	Limited	Biomarker	[32]
Leukemia	DISNAKFL	Limited	Biomarker	[31]
Lymphoid leukemia	DIS65TYQ	Limited	Biomarker	[31]

6 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 Lysine-specific demethylase 2B (KDM2B).	[33]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Lysine-specific demethylase 2B (KDM2B).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Lysine-specific demethylase 2B (KDM2B).	[45]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Lysine-specific demethylase 2B (KDM2B).	[46]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Lysine-specific demethylase 2B (KDM2B).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lysine-specific demethylase 2B (KDM2B).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lysine-specific demethylase 2B (KDM2B).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Lysine-specific demethylase 2B (KDM2B).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysine-specific demethylase 2B (KDM2B).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lysine-specific demethylase 2B (KDM2B).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Lysine-specific demethylase 2B (KDM2B).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Lysine-specific demethylase 2B (KDM2B).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Lysine-specific demethylase 2B (KDM2B).	[41]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Lysine-specific demethylase 2B (KDM2B).	[40]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Lysine-specific demethylase 2B (KDM2B).	[42]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Lysine-specific demethylase 2B (KDM2B).	[43]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Lysine-specific demethylase 2B (KDM2B).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lysine-specific demethylase 2B (KDM2B).	[47]

References

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