Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8UWRA3)

• DOT Name: CST complex subunit STN1 (STN1)
• Synonyms: Oligonucleotide/oligosaccharide-binding fold-containing protein 1; Suppressor of cdc thirteen homolog
• Gene Name: STN1
• Related Disease:
  Neoplasm
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Central nervous system neoplasm
  Cerebral palsy
  Cerebroretinal microangiopathy with calcifications and cysts 2
  Chronic obstructive pulmonary disease
  Coronary heart disease
  Depression
  Dyskeratosis congenita
  Endometriosis
  Epithelial ovarian cancer
  Glioma
  High blood pressure
  Isolated cleft palate
  Laryngeal carcinoma
  Lung cancer
  Lung neoplasm
  Matthew-Wood syndrome
  Melanoma
  Systemic sclerosis
  Tuberculosis
  Uterine fibroids
  Cutaneous melanoma
  Coats plus syndrome
  Basal cell carcinoma
  Basal cell neoplasm
  Colorectal carcinoma
  Coronary atherosclerosis
  Hereditary nonpolyposis colon cancer
  Non-insulin dependent diabetes
  Small lymphocytic lymphoma
• UniProt ID: STN1_HUMAN
• PDB ID: 4JOI; 4JQF; 6W6W; 7U5C; 8D0B; 8D0K; 8SOJ; 8SOK
• Pfam ID: PF09170 ; PF01336
• Sequence:
  MQPGSSRCEEETPSLLWGLDPVFLAFAKLYIRDILDMKESRQVPGVFLYNGHPIKQVDVL
  GTVIGVRERDAFYSYGVDDSTGVINCICWKKLNTESVSAAPSAARELSLTSQLKKLQETI
  EQKTKIEIGDTIRVRGSIRTYREEREIHATTYYKVDDPVWNIQIARMLELPTIYRKVYDQ
  PFHSSALEKEEALSNPGALDLPSLTSLLSEKAKEFLMENRVQSFYQQELEMVESLLSLAN
  QPVIHSASSDQVNFKKDTTSKAIHSIFKNAIQLLQEKGLVFQKDDGFDNLYYVTREDKDL
  HRKIHRIIQQDCQKPNHMEKGCHFLHILACARLSIRPGLSEAVLQQVLELLEDQSDIVST
  MEHYYTAF
• Function: Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation. However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha. The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins. Required for efficicient replication of the duplex region of the telomere. Promotes efficient replication of lagging-strand telomeres. Promotes general replication start following replication-fork stalling implicating new origin firing. May be in involved in C-strand fill-in during late S/G2 phase independent of its role in telomere duplex replication ; Component of the CST complex, a complex that binds to single-stranded DNA and is required to protect telomeres from DNA degradation. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. In addition to telomere protection, the CST complex has probably a more general role in DNA metabolism at non-telomeric sites.
• Reactome Pathway:
  Telomere C-strand synthesis initiation (R-HSA-174430)
  Polymerase switching on the C-strand of the telomere (R-HSA-174411)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[3]
Central nervous system neoplasm	DISFC18W	Strong	Genetic Variation	[4]
Cerebral palsy	DIS82ODL	Strong	Genetic Variation	[5]
Cerebroretinal microangiopathy with calcifications and cysts 2	DISZWLL2	Strong	Autosomal recessive	[6]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[7]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[8]
Depression	DIS3XJ69	Strong	Biomarker	[9]
Dyskeratosis congenita	DISSXV0K	Strong	Biomarker	[10]
Endometriosis	DISX1AG8	Strong	Genetic Variation	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Glioma	DIS5RPEH	Strong	Genetic Variation	[4]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[12]
Isolated cleft palate	DISV80CD	Strong	Genetic Variation	[5]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lung neoplasm	DISVARNB	Strong	Biomarker	[14]
Matthew-Wood syndrome	DISA7HR7	Strong	Genetic Variation	[15]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[16]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[17]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[18]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[19]
Cutaneous melanoma	DIS3MMH9	moderate	Genetic Variation	[20]
Coats plus syndrome	DIS11ELA	Supportive	Autosomal recessive	[21]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[22]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[22]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[23]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[24]
Hereditary nonpolyposis colon cancer	DISPA49R	Limited	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[24]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[25]

2 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 CST complex subunit STN1 (STN1).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CST complex subunit STN1 (STN1).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CST complex subunit STN1 (STN1).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CST complex subunit STN1 (STN1).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CST complex subunit STN1 (STN1).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CST complex subunit STN1 (STN1).	[30]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of CST complex subunit STN1 (STN1).	[31]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of CST complex subunit STN1 (STN1).	[32]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of CST complex subunit STN1 (STN1).	[33]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CST complex subunit STN1 (STN1).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of CST complex subunit STN1 (STN1).	[36]

References

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