Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ2FJ7Q)

• DOT Name: Protein Shroom2 (SHROOM2)
• Synonyms: Apical-like protein; Protein APXL
• Gene Name: SHROOM2
• Related Disease:
  Neural tube defect
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Ocular albinism
  Prostate cancer
  Prostate carcinoma
  X-linked recessive ocular albinism
  Metastatic malignant neoplasm
  Nasopharyngeal carcinoma
  Neurofibromatosis type 1
• UniProt ID: SHRM2_HUMAN
• PDB ID: 5F4Y; 5F5P
• Pfam ID: PF08688 ; PF08687 ; PF00595
• Sequence:
  MEGAEPRARPERLAEAETRAADGGRLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGS
  KAAAVDKLLAGDEIVGINDIGLSGFRQEAICLVKGSHKTLKLVVKRRSELGWRPHSWHAT
  KFSDSHPELAASPFTSTSGCPSWSGRHHASSSSHDLSSSWEQTNLQRTLDHFSSLGSVDS
  LDHPSSRLSVAKSNSSIDHLGSHSKRDSAYGSFSTSSSTPDHTLSKADTSSAENILYTVG
  LWEAPRQGGRQAQAAGDPQGSEEKLSCFPPRVPGDSGKGPRPEYNAEPKLAAPGRSNFGP
  VWYVPDKKKAPSSPPPPPPPLRSDSFAATKSHEKAQGPVFSEAAAAQHFTALAQAQPRGD
  RRPELTDRPWRSAHPGSLGKGSGGPGCPQEAHADGSWPPSKDGASSRLQASLSSSDVRFP
  QSPHSGRHPPLYSDHSPLCADSLGQEPGAASFQNDSPPQVRGLSSCDQKLGSGWQGPRPC
  VQGDLQAAQLWAGCWPSDTALGALESLPPPTVGQSPRHHLPQPEGPPDARETGRCYPLDK
  GAEGCSAGAQEPPRASRAEKASQRLAASITWADGESSRICPQETPLLHSLTQEGKRRPES
  SPEDSATRPPPFDAHVGKPTRRSDRFATTLRNEIQMHRAKLQKSRSTVALTAAGEAEDGT
  GRWRAGLGGGTQEGPLAGTYKDHLKEAQARVLRATSFKRRDLDPNPGDLYPESLEHRMGD
  PDTVPHFWEAGLAQPPSSTSGGPHPPRIGGRRRFTAEQKLKSYSEPEKMNEVGLTRGYSP
  HQHPRTSEDTVGTFADRWKFFEETSKPVPQRPAQKQALHGIPRDKPERPRTAGRTCEGTE
  PWSRTTSLGDSLNAHSAAEKAGTSDLPRRLGTFAEYQASWKEQRKPLEARSSGRCHSADD
  ILDVSLDPQERPQHVHGRSRSSPSTDHYKQEASVELRRQAGDPGEPREELPSAVRAEEGQ
  STPRQADAQCREGSPGSQQHPPSQKAPNPPTFSELSHCRGAPELPREGRGRAGTLPRDYR
  YSEESTPADLGPRAQSPGSPLHARGQDSWPVSSALLSKRPAPQRPPPPKREPRRYRATDG
  APADAPVGVLGRPFPTPSPASLDVYVARLSLSHSPSVFSSAQPQDTPKATVCERGSQHVS
  GDASRPLPEALLPPKQQHLRLQTATMETSRSPSPQFAPQKLTDKPPLLIQDEDSTRIERV
  MDNNTTVKMVPIKIVHSESQPEKESRQSLACPAEPPALPHGLEKDQIKTLSTSEQFYSRF
  CLYTRQGAEPEAPHRAQPAEPQPLGTQVPPEKDRCTSPPGLSYMKAKEKTVEDLKSEELA
  REIVGKDKSLADILDPSVKIKTTMDLMEGIFPKDEHLLEEAQQRRKLLPKIPSPRSTEER
  KEEPSVPAAVSLATNSTYYSTSAPKAELLIKMKDLQEQQEHEEDSGSDLDHDLSVKKQEL
  IESISRKLQVLREARESLLEDVQANTVLGAEVEAIVKGVCKPSEFDKFRMFIGDLDKVVN
  LLLSLSGRLARVENALNNLDDGASPGDRQSLLEKQRVLIQQHEDAKELKENLDRRERIVF
  DILANYLSEESLADYEHFVKMKSALIIEQRELEDKIHLGEEQLKCLLDSLQPERGK
• Function: May be involved in endothelial cell morphology changes during cell spreading. In the retinal pigment epithelium, may regulate the biogenesis of melanosomes and promote their association with the apical cell surface by inducing gamma-tubulin redistribution.
• Tissue Specificity: Abundant in retina and melanoma; also in brain, placenta, lung, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neural tube defect	DIS5J95E	Definitive	Genetic Variation	[1]
Colon cancer	DISVC52G	Strong	Genetic Variation	[2]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[2]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[2]
Ocular albinism	DIS5IHK1	Strong	Genetic Variation	[3]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[4]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[5]
X-linked recessive ocular albinism	DISI9S32	moderate	Biomarker	[6]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[7]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[7]
Neurofibromatosis type 1	DIS53JH9	Limited	Biomarker	[8]

4 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 Protein Shroom2 (SHROOM2).	[9]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Protein Shroom2 (SHROOM2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein Shroom2 (SHROOM2).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein Shroom2 (SHROOM2).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein Shroom2 (SHROOM2).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein Shroom2 (SHROOM2).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein Shroom2 (SHROOM2).	[12]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Protein Shroom2 (SHROOM2).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein Shroom2 (SHROOM2).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein Shroom2 (SHROOM2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein Shroom2 (SHROOM2).	[17]

References

• [1] Genetic and functional analysis of SHROOM1-4 in a Chinese neural tube defect cohort.Hum Genet. 2018 Mar;137(3):195-202. doi: 10.1007/s00439-017-1864-x. Epub 2018 Feb 8.
• [2] Association analyses identify 31 new risk loci for colorectal cancer susceptibility.Nat Commun. 2019 May 14;10(1):2154. doi: 10.1038/s41467-019-09775-w.
• [3] Congenital nasal pyriform aperture stenosis and ocular albinism co-occurring in a sibship with a maternally-inherited 97 kb Xp22.2 microdeletion.Am J Med Genet A. 2014 May;164A(5):1268-71. doi: 10.1002/ajmg.a.36415. Epub 2014 Jan 29.
• [4] Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.Nat Genet. 2013 Apr;45(4):385-91, 391e1-2. doi: 10.1038/ng.2560.
• [5] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [6] Cloning of a human homologue of the Xenopus laevis APX gene from the ocular albinism type 1 critical region.Hum Mol Genet. 1995 Mar;4(3):373-82. doi: 10.1093/hmg/4.3.373.
• [7] SHROOM2 inhibits tumor metastasis through RhoA-ROCK pathway-dependent and -independent mechanisms in nasopharyngeal carcinoma.Cell Death Dis. 2019 Jan 25;10(2):58. doi: 10.1038/s41419-019-1325-7.
• [8] Differences in MWCNT- and SWCNT-induced DNA methylation alterations in association with the nuclear deposition.Part Fibre Toxicol. 2018 Feb 9;15(1):11. doi: 10.1186/s12989-018-0244-6.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] 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.
• [18] 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.