Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPS2H0L)

• DOT Name: Epithelial membrane protein 2 (EMP2)
• Synonyms: EMP-2; Protein XMP
• Gene Name: EMP2
• Related Disease:
  Bladder transitional cell carcinoma
  Corneal neovascularization
  Melanoma
  Adult glioblastoma
  Advanced cancer
  Attention deficit hyperactivity disorder
  Breast cancer
  Breast carcinoma
  Charcot marie tooth disease
  Endometrium neoplasm
  Familial adenomatous polyposis
  Glioma
  Nasopharyngeal carcinoma
  Neoplasm
  Nephrotic syndrome, type 10
  Nephrotic syndrome, type 2
  Severe combined immunodeficiency
  Transitional cell carcinoma
  Urothelial carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Fetal growth restriction
  Metastatic malignant neoplasm
  Nephrotic syndrome
  Proliferative vitreoretinopathy
  Retinopathy
  Familial idiopathic steroid-resistant nephrotic syndrome
  Tuberculosis
  Glioblastoma multiforme
  Lung cancer
  Lung carcinoma
• UniProt ID: EMP2_HUMAN
• Pfam ID: PF00822
• Sequence:
  MLVLLAFIIAFHITSAALLFIATVDNAWWVGDEFFADVWRICTNNTNCTVINDSFQEYST
  LQAVQATMILSTILCCIAFFIFVLQLFRLKQGERFVLTSIIQLMSCLCVMIAASIYTDRR
  EDIHDKNAKFYPVTREGSYGYSYILAWVAFACTFISGMMYLILRKRK
• Function: Functions as a key regulator of cell membrane composition by regulating protein surface expression. Also, plays a role in regulation of processes including cell migration, cell proliferation, cell contraction and cell adhesion. Regulates transepithelial migration of neutrophils into the alveolar lumen, potentially via mediation of cell surface expression of adhesion markers and lipid raft formation. Negatively regulates caveolae formation by reducing CAV1 expression and CAV1 amount by increasing lysosomal degradation. Facilitates surface trafficking and formation of lipid rafts bearing GPI-anchor proteins. Regulates surface expression of MHC1 and ICAM1 proteins increasing susceptibility to T-cell mediated cytotoxicity. Regulates the plasma membrane expression of the integrin heterodimers ITGA6-ITGB1, ITGA5-ITGB3 and ITGA5-ITGB1 resulting in modulation of cell-matrix adhesion. Also regulates many processes through PTK2. Regulates blood vessel endothelial cell migration and angiogenesis by regulating VEGF protein expression through PTK2 activation. Regulates cell migration and cell contraction through PTK2 and SRC activation. Regulates focal adhesion density, F-actin conformation and cell adhesion capacity through interaction with PTK2. Positively regulates cell proliferation. Plays a role during cell death and cell blebbing. Promotes angiogenesis and vasculogenesis through induction of VEGFA via a HIF1A-dependent pathway. Also plays a role in embryo implantation by regulating surface trafficking of integrin heterodimer ITGA5-ITGB3. Plays a role in placental angiogenesis and uterine natural killer cell regulation at the maternal-fetal placental interface, however not required in the maternal tissues for a viable pregnancy. Involved in the early stages of embryogenic development and cardiogenesis, potentially via regulation of epithelial-mesenchymal transition timing. May play a role in glomerular filtration.
• Tissue Specificity: Expressed in ciliary body epithelia, sclera, cornea, and retinal pigment epithelium (at protein level) . Expressed in lung and endometrial tissue; expression is particularly abundant in secretory endometrium (at protein level) . Expressed in placental villous syncytiotrophoblasts and cytotrophoblasts and on the membrane of interstitial trophoblasts (at protein level) .
• KEGG Pathway: Focal adhesion (hsa04510)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder transitional cell carcinoma	DISNL46A	Definitive	Altered Expression	[1]
Corneal neovascularization	DISKOGZP	Definitive	Biomarker	[2]
Melanoma	DIS1RRCY	Definitive	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Charcot marie tooth disease	DIS3BT2L	Strong	Biomarker	[7]
Endometrium neoplasm	DIS6OS2L	Strong	Biomarker	[8]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Nephrotic syndrome, type 10	DISYDJ28	Strong	Autosomal recessive	[12]
Nephrotic syndrome, type 2	DISIRFO1	Strong	GermlineCausalMutation	[12]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Altered Expression	[13]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[13]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[13]
Endometrial cancer	DISW0LMR	moderate	Biomarker	[14]
Endometrial carcinoma	DISXR5CY	moderate	Biomarker	[14]
Fetal growth restriction	DIS5WEJ5	moderate	Biomarker	[15]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[14]
Nephrotic syndrome	DISSPSC2	moderate	Biomarker	[12]
Proliferative vitreoretinopathy	DISZTEK1	moderate	Altered Expression	[16]
Retinopathy	DISB4B0F	moderate	Altered Expression	[16]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[12]
Tuberculosis	DIS2YIMD	Disputed	Biomarker	[17]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[2]
Lung cancer	DISCM4YA	Limited	Biomarker	[18]
Lung carcinoma	DISTR26C	Limited	Biomarker	[18]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Epithelial membrane protein 2 (EMP2) affects the response to substance of Etoposide.	[39]
Mitomycin	DMH0ZJE	Approved	Epithelial membrane protein 2 (EMP2) affects the response to substance of Mitomycin.	[39]
Vinblastine	DM5TVS3	Approved	Epithelial membrane protein 2 (EMP2) affects the response to substance of Vinblastine.	[39]

22 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 Epithelial membrane protein 2 (EMP2).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Epithelial membrane protein 2 (EMP2).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Epithelial membrane protein 2 (EMP2).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Epithelial membrane protein 2 (EMP2).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Epithelial membrane protein 2 (EMP2).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Epithelial membrane protein 2 (EMP2).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Epithelial membrane protein 2 (EMP2).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the expression of Epithelial membrane protein 2 (EMP2).	[26]
Selenium	DM25CGV	Approved	Selenium increases the expression of Epithelial membrane protein 2 (EMP2).	[27]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Epithelial membrane protein 2 (EMP2).	[28]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Epithelial membrane protein 2 (EMP2).	[29]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Epithelial membrane protein 2 (EMP2).	[30]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Epithelial membrane protein 2 (EMP2).	[31]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Epithelial membrane protein 2 (EMP2).	[32]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Epithelial membrane protein 2 (EMP2).	[33]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Epithelial membrane protein 2 (EMP2).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Epithelial membrane protein 2 (EMP2).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Epithelial membrane protein 2 (EMP2).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Epithelial membrane protein 2 (EMP2).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Epithelial membrane protein 2 (EMP2).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Epithelial membrane protein 2 (EMP2).	[37]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Epithelial membrane protein 2 (EMP2).	[38]

References

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• [17] Biochemical characterization of recombinant guaA-encoded guanosine monophosphate synthetase (EC 6.3.5.2) from Mycobacterium tuberculosis H37Rv strain.Arch Biochem Biophys. 2012 Jan 1;517(1):1-11. doi: 10.1016/j.abb.2011.11.013. Epub 2011 Nov 18.
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• [34] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
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