Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR69LHT)

• DOT Name: Dynein light chain 1, cytoplasmic (DYNLL1)
• Synonyms: 8 kDa dynein light chain; DLC8; Dynein light chain LC8-type 1; Protein inhibitor of neuronal nitric oxide synthase; PIN
• Gene Name: DYNLL1
• Related Disease:
  Adenoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  B-cell neoplasm
  Benign prostatic hyperplasia
  Breast carcinoma
  Carcinoma
  Cardiac failure
  Cholangiocarcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Depression
  Erectile dysfunction
  Gastric cancer
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Malignant soft tissue neoplasm
  Medulloblastoma
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Plasma cell myeloma
  Prostate cancer
  Prostate neoplasm
  Prostatitis
  Renal cell carcinoma
  Sarcoma
  Stomach cancer
  Adult lymphoma
  Brain ischaemia
  Cardiac arrest
  Lymphoma
  Neuroblastoma
  Non-hodgkin lymphoma
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Pediatric lymphoma
  Squamous cell carcinoma
  High blood pressure
  Breast neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Prostate carcinoma
  Type-1/2 diabetes
• UniProt ID: DYL1_HUMAN
• PDB ID: 1CMI; 3ZKE; 3ZKF; 6GZJ; 6GZL; 6RLB; 6SC2; 7D35
• Pfam ID: PF01221
• Sequence:
  MCDRKAVIKNADMSEEMQQDSVECATQALEKYNIEKDIAAHIKKEFDKKYNPTWHCIVGR
  NFGSYVTHETKHFIYFYLGQVAILLFKSG
• Function: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.; Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1; Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity; Binds and inhibits the catalytic activity of neuronal nitric oxide synthase/NOS1.
• Tissue Specificity: Ubiquitous . Expressed in testis .
• KEGG Pathway:
  Motor proteins (hsa04814)
  Vasopressin-regulated water reabsorption (hsa04962)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)
  Macroautophagy (R-HSA-1632852)
  MHC class II antigen presentation (R-HSA-2132295)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  Intraflagellar transport (R-HSA-5620924)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Neutrophil degranulation (R-HSA-6798695)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)
  Mitotic Prometaphase (R-HSA-68877)
  AURKA Activation by TPX2 (R-HSA-8854518)
  HCMV Early Events (R-HSA-9609690)
  Aggrephagy (R-HSA-9646399)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Activation of BIM and translocation to mitochondria (R-HSA-111446)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[3]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[3]
B-cell neoplasm	DISVY326	Strong	Biomarker	[4]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Cardiac failure	DISDC067	Strong	Altered Expression	[8]
Cholangiocarcinoma	DIS71F6X	Strong	Posttranslational Modification	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[8]
Depression	DIS3XJ69	Strong	Biomarker	[13]
Erectile dysfunction	DISD8MTH	Strong	Therapeutic	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[17]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[18]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[19]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[20]
Plasma cell myeloma	DIS0DFZ0	Strong	Posttranslational Modification	[21]
Prostate cancer	DISF190Y	Strong	Biomarker	[22]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[23]
Prostatitis	DISL8OGN	Strong	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[10]
Sarcoma	DISZDG3U	Strong	Biomarker	[18]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[25]
Brain ischaemia	DIS9Q4RT	moderate	Biomarker	[26]
Cardiac arrest	DIS9DIA4	moderate	Biomarker	[26]
Lymphoma	DISN6V4S	moderate	Altered Expression	[25]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[27]
Non-hodgkin lymphoma	DISS2Y8A	moderate	Biomarker	[28]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[29]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[30]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[31]
High blood pressure	DISY2OHH	Disputed	Therapeutic	[32]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[33]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Genetic Variation	[34]
Liver cancer	DISDE4BI	Limited	Genetic Variation	[34]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[22]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[24]

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 Dynein light chain 1, cytoplasmic (DYNLL1).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Dynein light chain 1, cytoplasmic (DYNLL1).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Dynein light chain 1, cytoplasmic (DYNLL1).	[47]

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 Dynein light chain 1, cytoplasmic (DYNLL1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[40]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[42]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[43]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[39]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[39]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[44]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[46]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[48]
GW7604	DMCA4RM	Investigative	GW7604 increases the expression of Dynein light chain 1, cytoplasmic (DYNLL1).	[39]

References

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