Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX7DJR6)

• DOT Name: H/ACA ribonucleoprotein complex subunit DKC1 (DKC1)
• Synonyms: EC 5.4.99.-; CBF5 homolog; Dyskerin; Nopp140-associated protein of 57 kDa; Nucleolar protein NAP57; Nucleolar protein family A member 4; snoRNP protein DKC1
• Gene Name: DKC1
• Related Disease:
  B-cell neoplasm
  DKC1-related disorder
  Dyskeratosis congenita, X-linked
  Acute erythroid leukemia
  Acute myelogenous leukaemia
  Aplastic anemia
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Colorectal neoplasm
  Glioma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Hereditary hemochromatosis
  Lung cancer
  Lung carcinoma
  Melanoma
  Niemann-Pick disease, type C2
  Pancytopenia
  Plasma cell myeloma
  Pontocerebellar hypoplasia
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Bone osteosarcoma
  Dyskeratosis congenita, autosomal recessive 6
  Osteosarcoma
  Dyskeratosis congenita
  Hoyeraal-Hreidarsson syndrome
  Bone marrow failure syndrome
  Premature aging syndrome
  Pulmonary fibrosis
  Small lymphocytic lymphoma
• UniProt ID: DKC1_HUMAN
• PDB ID: 7BGB; 7TRC; 7V9A
• EC Number: 5.4.99.-
• Pfam ID: PF08068 ; PF01472 ; PF16198 ; PF01509
• Sequence:
  MADAEVIILPKKHKKKKERKSLPEEDVAEIQHAEEFLIKPESKVAKLDTSQWPLLLKNFD
  KLNVRTTHYTPLACGSNPLKREIGDYIRTGFINLDKPSNPSSHEVVAWIRRILRVEKTGH
  SGTLDPKVTGCLIVCIERATRLVKSQQSAGKEYVGIVRLHNAIEGGTQLSRALETLTGAL
  FQRPPLIAAVKRQLRVRTIYESKMIEYDPERRLGIFWVSCEAGTYIRTLCVHLGLLLGVG
  GQMQELRRVRSGVMSEKDHMVTMHDVLDAQWLYDNHKDESYLRRVVYPLEKLLTSHKRLV
  MKDSAVNAICYGAKIMLPGVLRYEDGIEVNQEIVVITTKGEAICMAIALMTTAVISTCDH
  GIVAKIKRVIMERDTYPRKWGLGPKASQKKLMIKQGLLDKHGKPTDSTPATWKQEYVDYS
  ESAKKEVVAEVVKAPQVVAEAAKTAKRKRESESESDETPPAAPQLIKKEKKKSKKDKKAK
  AGLESGAEPGDGDSDTTKKKKKKKKAKEVELVSE
• Function: [Isoform 1]: Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance. Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme ; [Isoform 3]: Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• Reactome Pathway:
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)
  Telomere Extension By Telomerase (R-HSA-171319)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Biomarker	[1]
DKC1-related disorder	DISP865O	Definitive	X-linked	[2]
Dyskeratosis congenita, X-linked	DISJ3Y69	Definitive	X-linked	[2]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Aplastic anemia	DISJRSC0	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Hereditary hemochromatosis	DISVG5MT	Strong	Genetic Variation	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[13]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[14]
Niemann-Pick disease, type C2	DISLYVZZ	Strong	Genetic Variation	[14]
Pancytopenia	DISVKEHV	Strong	Genetic Variation	[15]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[16]
Pontocerebellar hypoplasia	DISRICMU	Strong	Genetic Variation	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[8]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[8]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[8]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[18]
Dyskeratosis congenita, autosomal recessive 6	DISS84LS	moderate	Biomarker	[19]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[18]
Dyskeratosis congenita	DISSXV0K	Supportive	Autosomal dominant	[20]
Hoyeraal-Hreidarsson syndrome	DISAUR8F	Supportive	Autosomal dominant	[21]
Bone marrow failure syndrome	DISVUY1J	Limited	Biomarker	[4]
Premature aging syndrome	DIS51AGT	Limited	Genetic Variation	[22]
Pulmonary fibrosis	DISQKVLA	Limited	Biomarker	[23]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[35]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[36]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[37]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[26]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[28]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[30]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[31]
Menadione	DMSJDTY	Approved	Menadione affects the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[31]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[32]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[33]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[34]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[38]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[39]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[40]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1).	[41]

References

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