Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT21KEGX)

• DOT Name: PHD and RING finger domain-containing protein 1 (PHRF1)
• Gene Name: PHRF1
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Hypothyroidism
  Lupus
  Multiple sclerosis
  Neoplasm
  Non-small-cell lung cancer
  Rheumatoid arthritis
  Systemic sclerosis
• UniProt ID: PHRF1_HUMAN
• Pfam ID: PF00628 ; PF13639
• Sequence:
  MDDDSLDELVARSPGPDGHPQVGPADPAGDFEESSVGSSGDSGDDSDSEHGDGTDGEDEG
  ASEEEDLEDRSGSEDSEDDGETLLEVAGTQGKLEAAGSFNSDDDAESCPICLNAFRDQAV
  GTPENCAHYFCLDCIVEWSKNANSCPVDRTLFKCICIRAQFGGKILRKIPVENTKASEEE
  EDPTFCEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPECAAPGVVLAAD
  AGPVSEEEVSLLLADVVPTTSRLRPRAGRTRAIARTRQSERVRATVNRNRISTARRVQHT
  PGRLGSSLLDEAIEAVATGLSTAVYQRPLTPRTPARRKRKTRRRKKVPGRKKTPSGPSAK
  SKSSATRSKKRQHRVKKRRGKKVKSEATTRSRIARTLGLRRPVHSSCIPSVLKPVEPSLG
  LLRADIGAASLSLFGDPYELDPFDSSEELSANPLSPLSAKRRALSRSALQSHQPVARPVS
  VGLSRRRLPAAVPEPDLEEEPVPDLLGSILSGQSLLMLGSSDVIIHRDGSLSAKRAAPVS
  FQRNSGSLSRGEEGFKGCLQPRALPSGSPAQGPSGNRPQSTGLSCQGRSRTPARTAGAPV
  RLDLPAAPGAVQARNLSNGSVPGFRQSHSPWFNGTNKHTLPLASAASKISSRDSKPPCRS
  VVPGPPLKPAPRRTDISELPRIPKIRRDDGGGRRDAAPAHGQSIEIPSACISRLTGREGT
  GQPGRGTRAESEASSRVPREPGVHTGSSRPPAPSSHGSLAPLGPSRGKGVGSTFESFRIN
  IPGNMAHSSQLSSPGFCNTFRPVDDKEQRKENPSPLFSIKKTKQLRSEVYDPSDPTGSDS
  SAPGSSPERSGPGLLPSEITRTISINSPKAQTVQAVRCVTSYTVESIFGTEPEPPLGPSS
  AMSKLRGAVAAEGASDTEREEPTESQGLAARLRRPSPPEPWDEEDGASCSTFFGSEERTV
  TCVTVVEPEAPPSPDVLQAATHRVVELRPPSRSRSTSSSRSRKKAKRKRVSREHGRTRSG
  TRSESRDRSSRSASPSVGEERPRRQRSKAKSRRSSSDRSSSRERAKRKKAKDKSREHRRG
  PWGHSRRTSRSRSGSPGSSSYEHYESRKKKKRRSASRPRGRECSPTSSLERLCRHKHQRE
  RSHERPDRKESVAWPRDRRKRRSRSPSSEHRAREHRRPRSREKWPQTRSHSPERKGAVRE
  ASPAPLAQGEPGREDLPTRLPALGEAHVSPEVATADKAPLQAPPVLEVAAECEPDDLDLD
  YGDSVEAGHVFDDFSSDAVFIQLDDMSSPPSPESTDSSPERDFPLKPALPPASLAVAAIQ
  REVSLMHDEDPSQPPPLPEGTQEPHLLRPDAAEKAEAPSSPDVAPAGKEDSPSASGRVQE
  AARPEEVVSQTPLLRSRALVKRVTWNLQESESSAPAEDRAPRAPLHRPQKPREGAWDMED
  VAPTGVRQVFSELPFPSHVLPEPGFPDTDPSQVYSPGLPPAPAQPSSIPPCALVSQPTVQ
  FILQGSLPLVGCGAAQTLAPVPAALTPASEPASQATAASNSEEKTPAPRLAAEKTKKEEY
  MKKLHMQERAVEEVKLAIKPFYQKREVTKEEYKDILRKAVQKICHSKSGEINPVKVANLV
  KAYVDKYRHMRRHKKPEAGEEPPTQGAEG

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[3]
Lupus	DISOKJWA	Strong	Genetic Variation	[4]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[7]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PHD and RING finger domain-containing protein 1 (PHRF1).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of PHD and RING finger domain-containing protein 1 (PHRF1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PHD and RING finger domain-containing protein 1 (PHRF1).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of PHD and RING finger domain-containing protein 1 (PHRF1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of PHD and RING finger domain-containing protein 1 (PHRF1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PHD and RING finger domain-containing protein 1 (PHRF1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of PHD and RING finger domain-containing protein 1 (PHRF1).	[10]

References

• [1] Regulation of RIP3 by the transcription factor Sp1 and the epigenetic regulator UHRF1 modulates cancer cell necroptosis.Cell Death Dis. 2017 Oct 5;8(10):e3084. doi: 10.1038/cddis.2017.483.
• [2] Diagnostic and prognostic value of plasma and tissue ubiquitin-like, containing PHD and RING finger domains 1 in breast cancer patients.Cancer Sci. 2013 Feb;104(2):194-9. doi: 10.1111/cas.12052. Epub 2012 Dec 13.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study.Arthritis Rheum. 2011 Nov;63(11):3493-501. doi: 10.1002/art.30563.
• [5] Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.Ann Neurol. 2011 Dec;70(6):897-912. doi: 10.1002/ana.22609.
• [6] Overexpression of PHRF1 attenuates the proliferation and tumorigenicity of non-small cell lung cancer cells.Oncotarget. 2016 Sep 27;7(39):64360-64370. doi: 10.18632/oncotarget.11842.
• [7] Immunochip identifies novel, and replicates known, genetic risk loci for rheumatoid arthritis in black South Africans.Mol Med. 2014 Aug 14;20(1):341-9. doi: 10.2119/molmed.2014.00097.
• [8] A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.Hum Mol Genet. 2013 Oct 1;22(19):4021-9. doi: 10.1093/hmg/ddt248. Epub 2013 Jun 4.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.