Details of Drug Off-Target (DOT)

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

DOT Name Maltase-glucoamylase (MGAM)
Synonyms Alpha-1,4-glucosidase; EC 3.2.1.20
Gene Name MGAM
Related Disease
Tourette syndrome ( )
UniProt ID
MGA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2QLY; 2QMJ; 3CTT; 3L4T; 3L4U; 3L4V; 3L4W; 3L4X; 3L4Y; 3L4Z; 3TON; 3TOP
EC Number
3.2.1.20
Pfam ID
PF13802 ; PF01055 ; PF21365 ; PF00088
Sequence
MARKKLKKFTTLEIVLSVLLLVLFIISIVLIVLLAKESLKSTAPDPGTTGTPDPGTTGTP
DPGTTGTTHARTTGPPDPGTTGTTPVSAECPVVNELERINCIPDQPPTKATCDQRGCCWN
PQGAVSVPWCYYSKNHSYHVEGNLVNTNAGFTARLKNLPSSPVFGSNVDNVLLTAEYQTS
NRFHFKLTDQTNNRFEVPHEHVQSFSGNAAASLTYQVEISRQPFSIKVTRRSNNRVLFDS
SIGPLLFADQFLQLSTRLPSTNVYGLGEHVHQQYRHDMNWKTWPIFNRDTTPNGNGTNLY
GAQTFFLCLEDASGLSFGVFLMNSNAMEVVLQPAPAITYRTIGGILDFYVFLGNTPEQVV
QEYLELIGRPALPSYWALGFHLSRYEYGTLDNMREVVERNRAAQLPYDVQHADIDYMDER
RDFTYDSVDFKGFPEFVNELHNNGQKLVIIVDPAISNNSSSSKPYGPYDRGSDMKIWVNS
SDGVTPLIGEVWPGQTVFPDYTNPNCAVWWTKEFELFHNQVEFDGIWIDMNEVSNFVDGS
VSGCSTNNLNNPPFTPRILDGYLFCKTLCMDAVQHWGKQYDIHNLYGYSMAVATAEAAKT
VFPNKRSFILTRSTFAGSGKFAAHWLGDNTATWDDLRWSIPGVLEFNLFGIPMVGPDICG
FALDTPEELCRRWMQLGAFYPFSRNHNGQGYKDQDPASFGADSLLLNSSRHYLNIRYTLL
PYLYTLFFRAHSRGDTVARPLLHEFYEDNSTWDVHQQFLWGPGLLITPVLDEGAEKVMAY
VPDAVWYDYETGSQVRWRKQKVEMELPGDKIGLHLRGGYIFPTQQPNTTTLASRKNPLGL
IIALDENKEAKGELFWDNGETKDTVANKVYLLCEFSVTQNRLEVNISQSTYKDPNNLAFN
EIKILGTEEPSNVTVKHNGVPSQTSPTVTYDSNLKVAIITDIDLLLGEAYTVEWSIKIRD
EEKIDCYPDENGASAENCTARGCIWEASNSSGVPFCYFVNDLYSVSDVQYNSHGATADIS
LKSSVYANAFPSTPVNPLRLDVTYHKNEMLQFKIYDPNKNRYEVPVPLNIPSMPSSTPEG
QLYDVLIKKNPFGIEIRRKSTGTIIWDSQLLGFTFSDMFIRISTRLPSKYLYGFGETEHR
SYRRDLEWHTWGMFSRDQPPGYKKNSYGVHPYYMGLEEDGSAHGVLLLNSNAMDVTFQPL
PALTYRTTGGVLDFYVFLGPTPELVTQQYTELIGRPVMVPYWSLGFQLCRYGYQNDSEIA
SLYDEMVAAQIPYDVQYSDIDYMERQLDFTLSPKFAGFPALINRMKADGMRVILILDPAI
SGNETQPYPAFTRGVEDDVFIKYPNDGDIVWGKVWPDFPDVVVNGSLDWDSQVELYRAYV
AFPDFFRNSTAKWWKREIEELYNNPQNPERSLKFDGMWIDMNEPSSFVNGAVSPGCRDAS
LNHPPYMPHLESRDRGLSSKTLCMESQQILPDGSLVQHYNVHNLYGWSQTRPTYEAVQEV
TGQRGVVITRSTFPSSGRWAGHWLGDNTAAWDQLKKSIIGMMEFSLFGISYTGADICGFF
QDAEYEMCVRWMQLGAFYPFSRNHNTIGTRRQDPVSWDAAFVNISRNVLQTRYTLLPYLY
TLMQKAHTEGVTVVRPLLHEFVSDQVTWDIDSQFLLGPAFLVSPVLERNARNVTAYFPRA
RWYDYYTGVDINARGEWKTLPAPLDHINLHVRGGYILPWQEPALNTHLSRKNPLGLIIAL
DENKEAKGELFWDDGQTKDTVAKKVYLLCEFSVTQNHLEVTISQSTYKDPNNLAFNEIKI
LGMEEPSNVTVKHNGVPSQTSPTVTYDSNLKVAIITDINLFLGEAYTVEWSIKIRDEEKI
DCYPDENGDSAENCTARGCIWEASNSSGVPFCYFVNDLYSVSDVQYNSHGATADISLKSS
VHANAFPSTPVNPLRLDVTYHKNEMLQFKIYDPNNNRYEVPVPLNIPSVPSSTPEGQLYD
VLIKKNPFGIEIRRKSTGTIIWDSQLLGFTFNDMFIRISTRLPSKYLYGFGETEHTSYRR
DLEWHTWGMFSRDQPPGYKKNSYGVHPYYMGLEEDGSAHGVLLLNSNAMDVTFQPLPALT
YRTTGGVLDFYVFLGPTPELVTQQYTELIGRPVMVPYWSLGFQLCRYGYQNDSEISSLYD
EMVAAQIPYDVQYSDIDYMERQLDFTLSPKFAGFPALINRMKADGMRVILILDPAISGNE
TQPYPAFTRGVEDDVFIKYPNDGDIVWGKVWPDFPDVVVNGSLDWDSQVELYRAYVAFPD
FFRNSTAKWWKREIEELYNNPQNPERSLKFDGMWIDMNEPSSFVNGAVSPGCRDASLNHP
PYMPYLESRDRGLSSKTLCMESQQILPDGSPVQHYNVHNLYGWSQTRPTYEAVQEVTGQR
GVVITRSTFPSSGRWAGHWLGDNTAAWDQLKKSIIGMMEFSLFGISYTGADICGFFQDAE
YEMCVRWMQLGAFYPFSRNHNTIGTRRQDPVSWDVAFVNISRTVLQTRYTLLPYLYTLMH
KAHTEGVTVVRPLLHEFVSDQVTWDIDSQFLLGPAFLVSPVLERNARNVTAYFPRARWYD
YYTGVDINARGEWKTLPAPLDHINLHVRGGYILPWQEPALNTHLSRQKFMGFKIALDDEG
TAGGWLFWDDGQSIDTYGKGLYYLASFSASQNTMQSHIIFNNYITGTNPLKLGYIEIWGV
GSVPVTSVSISVSGMVITPSFNNDPTTQVLSIDVTDRNISLHNFTSLTWISTL
Function
Alpha-(1,4) exo-glucosidase involved in breakdown of dietary starch oligosaccharides in small intestine. Cleaves the non-reducing alpha-(1,4)-linked glucose residue in linear dextrins with retention of anomeric center stereochemistry. Mainly hydrolyzes short length oligomaltoses having two to seven glucose residues. Can cleave alpha-(1,2), alpha-(1,3) and alpha-(1,6) glycosidic linkages with lower efficiency, whereas beta glycosidic linkages are usually not hydrolyzed.
Tissue Specificity Broadly expressed. Highly expressed in small intestine. Expressed in granulocytes.
KEGG Pathway
Galactose metabolism (hsa00052 )
Starch and sucrose metabolism (hsa00500 )
Metabolic pathways (hsa01100 )
Carbohydrate digestion and absorption (hsa04973 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Digestion of dietary carbohydrate (R-HSA-189085 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Tourette syndrome DISX9D54 No Known Unknown [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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 Maltase-glucoamylase (MGAM). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Maltase-glucoamylase (MGAM). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Maltase-glucoamylase (MGAM). [4]
Permethrin DMZ0Q1G Approved Permethrin decreases the expression of Maltase-glucoamylase (MGAM). [5]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Maltase-glucoamylase (MGAM). [6]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Maltase-glucoamylase (MGAM). [7]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Maltase-glucoamylase (MGAM). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Maltase-glucoamylase (MGAM). [10]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Maltase-glucoamylase (MGAM). [11]
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⏷ Show the Full List of 9 Drug(s)
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 increases the methylation of Maltase-glucoamylase (MGAM). [8]
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References

1 De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
2 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.
3 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
4 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
5 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
6 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
7 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
8 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.
9 Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
10 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
11 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.