Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTN9B9O)

• DOT Name: PH and SEC7 domain-containing protein 3 (PSD3)
• Synonyms: Epididymis tissue protein Li 20mP; Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6 D; Exchange factor for ARF6 D; Hepatocellular carcinoma-associated antigen 67; Pleckstrin homology and SEC7 domain-containing protein 3
• Gene Name: PSD3
• Related Disease:
  Colon cancer
  Colon carcinoma
  Immune system disorder
  Non-insulin dependent diabetes
  Obesity
  Schizophrenia
  Epithelial ovarian cancer
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Astrocytoma
  Glioblastoma multiforme
  Amyotrophic lateral sclerosis type 1
  Antecubital pterygium syndrome
  Glioma
  Malignant glioma
  Mixed glioma
• UniProt ID: PSD3_HUMAN
• Pfam ID: PF15410 ; PF01369
• Sequence:
  MEGRSAAAETFVWVNNASAHSQSVAKAKYEFLFGRSEGKAPDTSDHGGSTLLPPNVTNEF
  PEYGTMEEGGEGLRASLEFDGEALPCHPQEQQGVQPLTGCHSGLDSVTEGPKDVREAPSQ
  SHLKEQSLQPIDSLISALKATEARIISGTLQATKVLDQDAVSSFSVQQVEKELDTASRKT
  QRVNKTLPAGQKNLPEIPLSAEVTTEESFYLSIQKDLTALLTGDTQAEISQIMNNGRKGA
  VCVQEPSCPLASLGSSAVTCHSAGSVGFLKEQRSALGREHPGGCDRSSSMGRPGRVKHVE
  FQGVEILWTGGDKRETQHPIDFETSLQRTASPDSKESSKVPRHLISSAGLCNSSSLTENV
  WDESWKAPSERPGTSSGTFSPVRLDESGEDEVFLQENKQHLEKTPKPERDRERISEQEEH
  VKGEDEDILGPGYTEDSTDVYSSQFETILDNTSLYYSAESLETLYSEPDSYFSFEMPLTP
  MIQQRIKEGGQFLERTSGGGHQDILSVSADGGIVMGYSSGVTNGLNDASDSIYTKGTPEI
  AFWGSNAGVKTTRLEAHSEMGSTEILEKETPENLSNGTSSNVEAAKRLAKRLYQLDRFKR
  SDVAKHLGKNNEFSKLVAEEYLKFFDFTGMTLDQSLRYFFKAFSLVGETQERERVLIHFS
  NRYFYCNPDTIASQDGVHCLTCAIMLLNTDLHGHVNIGKKMTCQEFIANLQGVNEGVDFS
  KDLLKALYNSIKNEKLEWAVDDEEKKKSPSESTEEKANGTHPKTISRIGSTTNPFLDIPH
  DPNAAVYKSGFLARKIHADMDGKKTPRGKRGWKTFYAVLKGTVLYLQKDEYKPEKALSEE
  DLKNAVSVHHALASKATDYEKKPNVFKLKTADWRVLLFQTQSPEEMQGWINKINCVAAVF
  SAPPFPAAIGSQKKFSRPLLPATTTKLSQEEQLKSHESKLKQITTELAEHRSYPPDKKVK
  AKDVDEYKLKDHYLEFEKTRYEMYVSILKEGGKELLSNDESEAAGLKKSHSSPSLNPDTS
  PITAKVKRNVSERKDHRPETPSIKQKVT
• Function: Guanine nucleotide exchange factor for ARF6.
• Tissue Specificity: Isoform 2 is expressed in epididymis (at protein level).
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Immune system disorder	DISAEGPH	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[2]
Obesity	DIS47Y1K	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Altered Expression	[4]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	moderate	Altered Expression	[4]
Astrocytoma	DISL3V18	Disputed	Altered Expression	[5]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[5]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Limited	Genetic Variation	[6]
Antecubital pterygium syndrome	DISKY9OW	Limited	Autosomal dominant	[7]
Glioma	DIS5RPEH	Limited	Biomarker	[5]
Malignant glioma	DISFXKOV	Limited	Biomarker	[5]
Mixed glioma	DIS64UY3	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	PH and SEC7 domain-containing protein 3 (PSD3) affects the response to substance of Methamphetamine.	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of PH and SEC7 domain-containing protein 3 (PSD3).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of PH and SEC7 domain-containing protein 3 (PSD3).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of PH and SEC7 domain-containing protein 3 (PSD3).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[17]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[18]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[19]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[20]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[21]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[22]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[23]
MGCD-0103	DM726HX	Phase 2	MGCD-0103 increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[25]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[23]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[23]
Oxamflatin	DM1TG3C	Terminated	Oxamflatin increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[29]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of PH and SEC7 domain-containing protein 3 (PSD3).	[23]

References

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• [20] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
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• [22] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
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• [26] 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.
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