Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBHV8NX)

• DOT Name: Prominin-1 (PROM1)
• Synonyms: Antigen AC133; Prominin-like protein 1; CD antigen CD133
• Gene Name: PROM1
• Related Disease:
  Inherited retinal dystrophy
  Retinitis pigmentosa 41
  Cone-rod dystrophy 12
  Retinal macular dystrophy type 2
  Cone-rod dystrophy
  Retinitis pigmentosa
  Stargardt disease
• UniProt ID: PROM1_HUMAN
• Pfam ID: PF05478
• Sequence:
  MALVLGSLLLLGLCGNSFSGGQPSSTDAPKAWNYELPATNYETQDSHKAGPIGILFELVH
  IFLYVVQPRDFPEDTLRKFLQKAYESKIDYDKPETVILGLKIVYYEAGIILCCVLGLLFI
  ILMPLVGYFFCMCRCCNKCGGEMHQRQKENGPFLRKCFAISLLVICIIISIGIFYGFVAN
  HQVRTRIKRSRKLADSNFKDLRTLLNETPEQIKYILAQYNTTKDKAFTDLNSINSVLGGG
  ILDRLRPNIIPVLDEIKSMATAIKETKEALENMNSTLKSLHQQSTQLSSSLTSVKTSLRS
  SLNDPLCLVHPSSETCNSIRLSLSQLNSNPELRQLPPVDAELDNVNNVLRTDLDGLVQQG
  YQSLNDIPDRVQRQTTTVVAGIKRVLNSIGSDIDNVTQRLPIQDILSAFSVYVNNTESYI
  HRNLPTLEEYDSYWWLGGLVICSLLTLIVIFYYLGLLCGVCGYDRHATPTTRGCVSNTGG
  VFLMVGVGLSFLFCWILMIIVVLTFVFGANVEKLICEPYTSKELFRVLDTPYLLNEDWEY
  YLSGKLFNKSKMKLTFEQVYSDCKKNRGTYGTLHLQNSFNISEHLNINEHTGSISSELES
  LKVNLNIFLLGAAGRKNLQDFAACGIDRMNYDSYLAQTGKSPAGVNLLSFAYDLEAKANS
  LPPGNLRNSLKRDAQTIKTIHQQRVLPIEQSLSTLYQSVKILQRTGNGLLERVTRILASL
  DFAQNFITNNTSSVIIEETKKYGRTIIGYFEHYLQWIEFSISEKVASCKPVATALDTAVD
  VFLCSYIIDPLNLFWFGIGKATVFLLPALIFAVKLAKYYRRMDSEDVYDDVETIPMKNME
  NGNNGYHKDHVYGIHNPVMTSPSQH
• Function: May play a role in cell differentiation, proliferation and apoptosis. Binds cholesterol in cholesterol-containing plasma membrane microdomains and may play a role in the organization of the apical plasma membrane in epithelial cells. During early retinal development acts as a key regulator of disk morphogenesis. Involved in regulation of MAPK and Akt signaling pathways. In neuroblastoma cells suppresses cell differentiation such as neurite outgrowth in a RET-dependent manner.
• Tissue Specificity: Isoform 1 is selectively expressed on CD34 hematopoietic stem and progenitor cells in adult and fetal bone marrow, fetal liver, cord blood and adult peripheral blood. Isoform 1 is not detected on other blood cells. Isoform 1 is also expressed in a number of non-lymphoid tissues including retina, pancreas, placenta, kidney, liver, lung, brain and heart. Found in saliva within small membrane particles. Isoform 2 is predominantly expressed in fetal liver, skeletal muscle, kidney, and heart as well as adult pancreas, kidney, liver, lung, and placenta. Isoform 2 is highly expressed in fetal liver, low in bone marrow, and barely detectable in peripheral blood. Isoform 2 is expressed on hematopoietic stem cells and in epidermal basal cells (at protein level). Expressed in adult retina by rod and cone photoreceptor cells (at protein level).
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inherited retinal dystrophy	DISGGL77	Definitive	Autosomal recessive	[1]
Retinitis pigmentosa 41	DIS70Y7U	Definitive	Autosomal recessive	[2]
Cone-rod dystrophy 12	DISOSKVC	Strong	Autosomal recessive	[3]
Retinal macular dystrophy type 2	DISX7FZJ	Strong	Autosomal dominant	[3]
Cone-rod dystrophy	DISY9RWN	Supportive	Autosomal dominant	[4]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[5]
Stargardt disease	DISPXOTO	Supportive	Autosomal dominant	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Prominin-1 (PROM1) decreases the response to substance of Paclitaxel.	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Prominin-1 (PROM1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prominin-1 (PROM1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Prominin-1 (PROM1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Prominin-1 (PROM1).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Prominin-1 (PROM1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Prominin-1 (PROM1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Prominin-1 (PROM1).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Prominin-1 (PROM1).	[12]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Prominin-1 (PROM1).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Prominin-1 (PROM1).	[14]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Prominin-1 (PROM1).	[15]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Prominin-1 (PROM1).	[16]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of Prominin-1 (PROM1).	[17]
Melatonin	DMKWFBT	Approved	Melatonin decreases the expression of Prominin-1 (PROM1).	[18]
Crizotinib	DM4F29C	Approved	Crizotinib decreases the expression of Prominin-1 (PROM1).	[19]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR increases the expression of Prominin-1 (PROM1).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Prominin-1 (PROM1).	[21]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Prominin-1 (PROM1).	[22]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Prominin-1 (PROM1).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Prominin-1 (PROM1).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Prominin-1 (PROM1).	[26]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Prominin-1 (PROM1).	[28]
Apigenin	DMI3491	Investigative	Apigenin decreases the expression of Prominin-1 (PROM1).	[29]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE decreases the expression of Prominin-1 (PROM1).	[30]
Ginsenoside RG3	DMFN58T	Investigative	Ginsenoside RG3 decreases the expression of Prominin-1 (PROM1).	[31]
Eckol	DMIVY0Q	Investigative	Eckol decreases the expression of Prominin-1 (PROM1).	[32]
SD-208	DMQXUYH	Investigative	SD-208 decreases the expression of Prominin-1 (PROM1).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Prominin-1 (PROM1).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Prominin-1 (PROM1).	[27]

References

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