Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCIM29R)

DOT Name	Alkaline phosphatase, germ cell type (ALPG)
Synonyms	EC 3.1.3.1; ALP-1; Alkaline phosphatase Nagao isozyme; Alkaline phosphatase, placental-like; Germ cell alkaline phosphatase; GCAP; Placental alkaline phosphatase-like; PLAP-like
Gene Name	ALPG
Related Disease	Gastric adenocarcinoma ( ) Gastric cancer ( ) Stomach cancer ( ) Adult germ cell tumor ( ) Adult teratoma ( ) Blindness ( ) Choriocarcinoma ( ) Colitis ( ) Colon cancer ( ) Colon carcinoma ( ) Cone-rod dystrophy ( ) Embryonal neoplasm ( ) Germ cell tumour ( ) Seminoma ( ) Teratoma ( ) Neoplasm ( ) Pancreatic cancer ( ) Pancreatic ductal carcinoma ( ) Cryptorchidism ( ) Germ cell tumor ( )
UniProt ID	PPBN_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.1.3.1
Pfam ID	PF00245
Sequence	MQGPWVLLLLGLRLQLSLGIIPVEEENPDFWNRQAAEALGAAKKLQPAQTAAKNLIIFLG DGMGVSTVTAARILKGQKKDKLGPETFLAMDRFPYVALSKTYSVDKHVPDSGATATAYLC GVKGNFQTIGLSAAARFNQCNTTRGNEVISVMNRAKKAGKSVGVVTTTRVQHASPAGAYA HTVNRNWYSDADVPASARQEGCQDIATQLISNMDIDVILGGGRKYMFPMGTPDPEYPDDY SQGGTRLDGKNLVQEWLAKHQGARYVWNRTELLQASLDPSVTHLMGLFEPGDMKYEIHRD STLDPSLMEMTEAALLLLSRNPRGFFLFVEGGRIDHGHHESRAYRALTETIMFDDAIERA GQLTSEEDTLSLVTADHSHVFSFGGYPLRGSSIFGLAPGKARDRKAYTVLLYGNGPGYVL KDGARPDVTESESGSPEYRQQSAVPLDGETHAGEDVAVFARGPQAHLVHGVQEQTFIAHV MAFAACLEPYTACDLAPRAGTTDAAHPGPSVVPALLPLLAGTLLLLGTATAP
Function	Alkaline phosphatase that can hydrolyze various phosphate compounds.
Tissue Specificity	Trace amounts in the testis and thymus, and in elevated amounts in germ cell tumors.
KEGG Pathway	Thiamine metabolism (hsa00730 ) Folate biosynthesis (hsa00790 ) Metabolic pathways (hsa01100 ) Biosynthesis of cofactors (hsa01240 )
Reactome Pathway	Post-translational modification (R-HSA-163125 )

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Gastric adenocarcinoma	DISWWLTC	Definitive	Altered Expression	[1]
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Adult germ cell tumor	DISJUCQ7	Strong	Biomarker	[2]
Adult teratoma	DISBY81U	Strong	Altered Expression	[3]
Blindness	DISTIM10	Strong	Genetic Variation	[4]
Choriocarcinoma	DISDBVNL	Strong	Altered Expression	[5]
Colitis	DISAF7DD	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Genetic Variation	[7]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[7]
Cone-rod dystrophy	DISY9RWN	Strong	Biomarker	[8]
Embryonal neoplasm	DIS5MQSB	Strong	Biomarker	[9]
Germ cell tumour	DISOF3TK	Strong	Biomarker	[2]
Seminoma	DIS3J8LJ	Strong	Biomarker	[10]
Teratoma	DIS6ICY4	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	moderate	Biomarker	[1]
Pancreatic cancer	DISJC981	Disputed	Biomarker	[11]
Pancreatic ductal carcinoma	DIS26F9Q	Disputed	Biomarker	[11]
Cryptorchidism	DISYUD2P	Limited	Biomarker	[12]
Germ cell tumor	DIS62070	Limited	Biomarker	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Alkaline phosphatase, germ cell type (ALPG) affects the response to substance of Etoposide.	[21]
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1 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 Alkaline phosphatase, germ cell type (ALPG).	[13]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Alkaline phosphatase, germ cell type (ALPG).	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Alkaline phosphatase, germ cell type (ALPG).	[15]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Alkaline phosphatase, germ cell type (ALPG).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Alkaline phosphatase, germ cell type (ALPG).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Alkaline phosphatase, germ cell type (ALPG).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Alkaline phosphatase, germ cell type (ALPG).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Alkaline phosphatase, germ cell type (ALPG).	[19]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Alkaline phosphatase, germ cell type (ALPG).	[20]
Daidzein	DMRFTJX	Investigative	Daidzein increases the expression of Alkaline phosphatase, germ cell type (ALPG).	[14]
Hydroxyestradiol	DMJXQME	Investigative	Hydroxyestradiol increases the activity of Alkaline phosphatase, germ cell type (ALPG).	[14]
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References

1	High expression of ALPPL2 is associated with poor prognosis in gastric cancer.Hum Pathol. 2019 Apr;86:49-56. doi: 10.1016/j.humpath.2018.11.019. Epub 2018 Nov 26.
2	The Y-encoded TSPY protein: a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors.Hum Pathol. 2007 Oct;38(10):1470-81. doi: 10.1016/j.humpath.2007.03.011. Epub 2007 May 22.
3	Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs.Folia Histochem Cytobiol. 2015;53(3):177-88. doi: 10.5603/FHC.a2015.0020. Epub 2015 Aug 26.
4	Functional EF-hands in neuronal calcium sensor GCAP2 determine its phosphorylation state and subcellular distribution in vivo, and are essential for photoreceptor cell integrity.PLoS Genet. 2014 Jul 24;10(7):e1004480. doi: 10.1371/journal.pgen.1004480. eCollection 2014 Jul.
5	Differential expression and butyrate response of human alkaline phosphatase genes are mediated by upstream DNA elements.Biochemistry. 1996 Jul 30;35(30):9807-14. doi: 10.1021/bi9602223.
6	Structural characterization of water-soluble polysaccharide from Arctium lappa and its effects on colitis mice.Carbohydr Polym. 2019 Jun 1;213:89-99. doi: 10.1016/j.carbpol.2019.02.090. Epub 2019 Feb 27.
7	Molecular cloning of complementary DNAs encoding alkaline phosphatase in human colon cancer cells.Cancer Res. 1990 Feb 15;50(4):1085-91.
8	Biochemical analysis of a dimerization domain mutation in RetGC-1 associated with dominant cone-rod dystrophy.Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9039-44. doi: 10.1073/pnas.96.16.9039.
9	Identification of two molecular groups of seminomas by using expression and tissue microarrays.Clin Cancer Res. 2005 Aug 15;11(16):5722-9. doi: 10.1158/1078-0432.CCR-05-0533.
10	Regenerating I messenger RNA and protein expression in the failing human testis: a potential molecular prognostic marker of seminoma.Hum Pathol. 2011 Dec;42(12):1841-8. doi: 10.1016/j.humpath.2010.05.033. Epub 2011 Jun 17.
11	ALPPL2 Is a Potential Diagnostic Biomarker for Pancreatic Cancer-Derived Extracellular Vesicles.Mol Ther Methods Clin Dev. 2019 Sep 12;15:204-210. doi: 10.1016/j.omtm.2019.08.016. eCollection 2019 Dec 13.
12	Positive Oct -3/4 and D2-40 Immunohistochemical Expression in Germ Cells and Suspected Histology Pattern of Intratubular Germ Cell Neoplasia in Boys with Cryptorchidism Vanish after the Age of 2 Years.Eur J Pediatr Surg. 2017 Aug;27(4):313-318. doi: 10.1055/s-0036-1592137. Epub 2016 Sep 8.
13	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.
14	Estrogenic and genotoxic potential of equol and two hydroxylated metabolites of Daidzein in cultured human Ishikawa cells. Toxicol Lett. 2005 Jul 28;158(1):72-86. doi: 10.1016/j.toxlet.2005.02.011. Epub 2005 Apr 11.
15	Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
16	The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
17	Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
18	Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
19	Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
20	Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
21	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.