Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4IMC0X)

• DOT Name: Sesquipedalian-1 (PHETA1)
• Synonyms: Ses1; 27 kDa inositol polyphosphate phosphatase-interacting protein A; IPIP27A; PH domain-containing endocytic trafficking adaptor 1
• Gene Name: PHETA1
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
  Bipolar disorder
  Dent disease
  Oculocerebrorenal syndrome
  Keratoconjunctivitis sicca
• UniProt ID: SESQ1_HUMAN
• PDB ID: 3QIS
• Pfam ID: PF00169
• Sequence:
  MKLNERSLAFYATCDAPVDNAGFLYKKGGRHAAYHRRWFVLRGNMLFYFEDAASREPVGV
  IILEGCTVELVEAAEEFAFAVRFAGTRARTYVLAAESQDAMEGWVKALSRASFDYLRLVV
  RELEQQLAAVRGGGGMALPQPQPQSLPLPPSLPSALAPVPSLPSAPAPVPALPLPRRPSA
  LPPKENGCAVWSTEATFRPGPEPPPPPPRRRASAPHGPLDMAPFARLHECYGQEIRALRG
  QWLSSRVQP
• Function: Plays a role in endocytic trafficking. Required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Dent disease	DISRDLFN	Strong	Biomarker	[3]
Oculocerebrorenal syndrome	DIS8TEDY	Strong	Biomarker	[3]
Keratoconjunctivitis sicca	DISNOENH	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sesquipedalian-1 (PHETA1).	[5]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Sesquipedalian-1 (PHETA1).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Sesquipedalian-1 (PHETA1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sesquipedalian-1 (PHETA1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sesquipedalian-1 (PHETA1).	[9]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Sesquipedalian-1 (PHETA1).	[6]

References

• [1] Highly Expressed Genes in Rapidly Proliferating Tumor Cells as New Targets for Colorectal Cancer Treatment.Clin Cancer Res. 2015 Aug 15;21(16):3695-704. doi: 10.1158/1078-0432.CCR-14-2457. Epub 2015 May 5.
• [2] Linkage disequilibrium mapping of bipolar affective disorder at 12q23-q24 provides evidence for association at CUX2 and FLJ32356.Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):38-45. doi: 10.1002/ajmg.b.30081.
• [3] The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway.Mol Biol Cell. 2011 Mar 1;22(5):606-23. doi: 10.1091/mbc.E10-08-0730. Epub 2011 Jan 13.
• [4] Incidence and Risk Factors of Dry Eye in a Spanish Adult Population: 11-Year Follow-Up From the Salns Eye Study.Cornea. 2018 Dec;37(12):1527-1534. doi: 10.1097/ICO.0000000000001713.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.