Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9I1XUO)

• DOT Name: Inactive cell surface hyaluronidase CEMIP2 (CEMIP2)
• Synonyms: Cell migration-inducing hyaluronidase 2; Transmembrane protein 2
• Gene Name: CEMIP2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Polycystic kidney disease
• UniProt ID: CEIP2_HUMAN
• PDB ID: 8C6I
• Pfam ID: PF10162 ; PF15711
• Sequence:
  MYATDSRGHSPAFLQPQNGNSRHPSGYVPGKVVPLRPPPPPKSQASAKFTSIRREDRATF
  AFSPEEQQAQRESQKQKRHKNTFICFAITSFSFFIALAIILGISSKYAPDENCPDQNPRL
  RNWDPGQDSAKQVVIKEGDMLRLTSDATVHSIVIQDGGLLVFGDNKDGSRNITLRTHYIL
  IQDGGALHIGAEKCRYKSKATITLYGKSDEGESMPTFGKKFIGVEAGGTLELHGARKASW
  TLLARTLNSSGLPFGSYTFEKDFSRGLNVRVIDQDTAKILESERFDTHEYRNESRRLQEF
  LRFQDPGRIVAIAVGDSAAKSLLQGTIQMIQERLGSELIQGLGYRQAWALVGVIDGGSTS
  CNESVRNYENHSSGGKALAQREFYTVDGQKFSVTAYSEWIEGVSLSGFRVEVVDGVKLNL
  LDDVSSWKPGDQIVVASTDYSMYQAEEFTLLPCSECSHFQVKVKETPQFLHMGEIIDGVD
  MRAEVGILTRNIVIQGEVEDSCYAENQCQFFDYDTFGGHIMIMKNFTSVHLSYVELKHMG
  QQQMGRYPVHFHLCGDVDYKGGYRHATFVDGLSIHHSFSRCITVHGTNGLLIKDTIGFDT
  LGHCFFLEDGIEQRNTLFHNLGLLTKPGTLLPTDRNNSMCTTMRDKVFGNYIPVPATDCM
  AVSTFWIAHPNNNLINNAAAGSQDAGIWYLFHKEPTGESSGLQLLAKPELTPLGIFYNNR
  VHSNFKAGLFIDKGVKTTNSSAADPREYLCLDNSARFRPHQDANPEKPRVAALIDRLIAF
  KNNDNGAWVRGGDIIVQNSAFADNGIGLTFASDGSFPSDEGSSQEVSESLFVGESRNYGF
  QGGQNKYVGTGGIDQKPRTLPRNRTFPIRGFQIYDGPIHLTRSTFKKYVPTPDRYSSAIG
  FLMKNSWQITPRNNISLVKFGPHVSLNVFFGKPGPWFEDCEMDGDKNSIFHDIDGSVTGY
  KDAYVGRMDNYLIRHPSCVNVSKWNAVICSGTYAQVYVQTWSTQNLSMTITRDEYPSNPM
  VLRGINQKAAFPQYQPVVMLEKGYTIHWNGPAPRTTFLYLVNFNKNDWIRVGLCYPSNTS
  FQVTFGYLQRQNGSLSKIEEYEPVHSLEELQRKQSERKFYFDSSTGLLFLYLKAKSHRHG
  HSYCSSQGCERVKIQAATDSKDISNCMAKAYPQYYRKPSVVKRMPAMLTGLCQGCGTRQV
  VFTSDPHKSYLPVQFQSPDKAETQRGDPSVISVNGTDFTFRSAGVLLLVVDPCSVPFRLT
  EKTVFPLADVSRIEEYLKTGIPPRSIVLLSTRGEIKQLNISHLLVPLGLAKPAHLYDKGS
  TIFLGFSGNFKPSWTKLFTSPAGQGLGVLEQFIPLQLDEYGCPRATTVRRRDLELLKQAS
  KAH
• Function: Unlike its mouse ortholog has no catalytic hyaluronic acid-degrading activity, but acts as a regulator of hyaluronan (HA) metabolism through regulation of expression of CEMIP and HAS2, two enzymes involved in HA depolymerization and HA synthesis, respectively.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[12]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[13]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[14]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[14]
Bleomycin	DMNER5S	Approved	Bleomycin decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[17]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[20]

1 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 decreases the methylation of Inactive cell surface hyaluronidase CEMIP2 (CEMIP2).	[16]

References

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• [2] Identification of Biomarkers for PKD1 Using Urinary Exosomes.J Am Soc Nephrol. 2015 Jul;26(7):1661-70. doi: 10.1681/ASN.2014040354. Epub 2014 Dec 4.
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• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [14] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [17] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [20] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.