Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8I8ZHH)

• DOT Name: Cilia- and flagella-associated protein 45 (CFAP45)
• Synonyms: Coiled-coil domain-containing protein 19; Nasopharyngeal epithelium-specific protein 1
• Gene Name: CFAP45
• Related Disease:
  Bladder cancer
  Malignant mesothelioma
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Colorectal carcinoma
  Nasopharyngeal carcinoma
• UniProt ID: CFA45_HUMAN
• PDB ID: 7UNG; 8J07
• Pfam ID: PF13868
• Sequence:
  MPLSTAGILSSSSAASNRSRNKARYRTKAVSSEVDESLFGDIKSPAQGQSDSPIVLLRDK
  HTLQKTLTALGLDRKPETIQLITRDMVRELIVPTEDPSGESLIISPEEFERIKWASHVLT
  REELEARDQAFKKEKEATMDAVMTRKKIMKQKEMVWNNNKKLSDLEEVAKERAQNLLQRA
  NKLRMEQEEELKDMSKIILNAKCHAIRDAQILEKQQIQKELDTEEKRLDQMMEVERQKSI
  QRQEELERKRREERIRGRRQIVEQMEKNQEERSLLAEQREQEKEQMLEYMEQLQEEDLKD
  MERRQQQKLKMQAEIKRINDENQKQKAELLAQEKLADQMVMEFTKKKMAREAEFEAEQER
  IRREKEKEIARLRAMQEKAQDYQAEQDALRAKRNQEVADREWRRKEKENARKKMETEAEL
  RKSRLEQVAFKEHALAVQVQRDRDEFERILRAQREQIEKERLEEEKKATGRLQHANELRR
  QVRENQQKEVQNRIATFEEGRRLKEEAQKRRERIDEIKRKKLEELRATGLPEKYCIEAER
  KANILPATSVN
• Function: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. It is an AMP-binding protein that may facilitate dynein ATPase-dependent ciliary and flagellar beating via adenine nucleotide homeostasis. May function as a donor of AMP to AK8 and hence promote ADP production.
• Tissue Specificity: Expressed in respiratory cells and in sperm (at protein level) . Expressed in nasopharyngeal epithelium and trachea .

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[3]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[4]

1 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 Cilia- and flagella-associated protein 45 (CFAP45).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cilia- and flagella-associated protein 45 (CFAP45).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cilia- and flagella-associated protein 45 (CFAP45).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Cilia- and flagella-associated protein 45 (CFAP45).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Cilia- and flagella-associated protein 45 (CFAP45).	[9]

References

• [1] Long noncoding RNA MAGI2-AS3 regulates CCDC19 expression by sponging miR-15b-5p and suppresses bladder cancer progression.Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):231-235. doi: 10.1016/j.bbrc.2018.11.013. Epub 2018 Nov 12.
• [2] Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations.Nat Genet. 2016 Apr;48(4):407-16. doi: 10.1038/ng.3520. Epub 2016 Feb 29.
• [3] VPS33B negatively modulated by nicotine functions as a tumor suppressor in colorectal cancer.Int J Cancer. 2020 Jan 15;146(2):496-509. doi: 10.1002/ijc.32429. Epub 2019 Jun 19.
• [4] VPS33B interacts with NESG1 to modulate EGFR/PI3K/AKT/c-Myc/P53/miR-133a-3p signaling and induce 5-fluorouracil sensitivity in nasopharyngeal carcinoma.Cell Death Dis. 2019 Apr 3;10(4):305. doi: 10.1038/s41419-019-1457-9.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.