Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT44TM7D)

DOT Name	Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1)
Synonyms	EC 3.2.1.113; HMIC; Mannosidase alpha class 1C member 1; Processing alpha-1,2-mannosidase IC; Alpha-1,2-mannosidase IC
Gene Name	MAN1C1
Related Disease	Neoplasm ( ) Obstructive sleep apnea ( ) Schizophrenia ( ) Clear cell renal carcinoma ( ) Pulmonary emphysema ( ) Renal cell carcinoma ( ) Common variable immunodeficiency ( )
UniProt ID	MA1C1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.2.1.113
Pfam ID	PF01532
Sequence	MLMRKVPGFVPASPWGLRLPQKFLFLLFLSGLVTLCFGALFLLPHSSRLKRLFLAPRTQQ PGLEVVAEIAGHAPAREQEPPPNPAPAAPAPGEDDPSSWASPRRRKGGLRRTRPTGPREE ATAARGNSIPASRPGDEGVPFRFDFNAFRSRLRHPVLGTRADESQEPQSQVRAQREKIKE MMQFAWQSYKRYAMGKNELRPLTKDGYEGNMFGGLSGATVIDSLDTLYLMELKEEFQEAK AWVGESFHLNVSGEASLFEVNIRYIGGLLSAFYLTGEEVFRIKAIRLGEKLLPAFNTPTG IPKGVVSFKSGNWGWATAGSSSILAEFGSLHLEFLHLTELSGNQVFAEKVRNIRKVLRKI EKPFGLYPNFLSPVSGNWVQHHVSVGGLGDSFYEYLIKSWLMSGKTDMEAKNMYYEALEA IETYLLNVSPGGLTYIAEWRGGILDHKMGHLACFSGGMIALGAEDAKEEKRAHYRELAAQ ITKTCHESYARSDTKLGPEAFWFNSGREAVATQLSESYYILRPEVVESYMYLWRQTHNPI YREWGWEVVLALEKYCRTEAGFSGIQDVYSSTPNHDNKQQSFFLAETLKYLYLLFSEDDL LSLEDWVFNTEAHPLPVNHSDSSGRAWGRH
Function	Involved in the maturation of Asn-linked oligosaccharides. Trim alpha-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce first Man(8)GlcNAc(2) then Man(6)GlcNAc and a small amount of Man(5)GlcNAc.
Tissue Specificity	Expressed in most tissues with the exception of lung, muscle and pancreas. Highly expressed in placenta.
KEGG Pathway	N-Glycan biosynthesis (hsa00510 ) Various types of N-glycan biosynthesis (hsa00513 ) Metabolic pathways (hsa01100 ) Protein processing in endoplasmic reticulum (hsa04141 )
Reactome Pathway	Progressive trimming of alpha-1,2-linked mannose residues from Man9/8/7GlcNAc2 to produce Man5GlcNAc2 (R-HSA-964827 ) Intra-Golgi traffic (R-HSA-6811438 )
BioCyc Pathway	MetaCyc:HS04162-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[1]
Pulmonary emphysema	DIS5M7HZ	moderate	Genetic Variation	[4]
Renal cell carcinoma	DISQZ2X8	moderate	Genetic Variation	[1]
Common variable immunodeficiency	DISHE7JQ	Limited	Genetic Variation	[5]
------------------------------------------------------------------------------------


⏷ Show the Full List of 7 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[6]
------------------------------------------------------------------------------------

14 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 Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[14]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[17]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC (MAN1C1).	[19]
------------------------------------------------------------------------------------


⏷ Show the Full List of 14 Drug(s)

References

1	-1,2-Mannosidase MAN1C1 Inhibits Proliferation and Invasion of Clear Cell Renal Cell Carcinoma.J Cancer. 2018 Nov 24;9(24):4618-4626. doi: 10.7150/jca.27673. eCollection 2018.
2	Nurse vs. physician-led care for obstructive sleep apnoea: A systematic review and meta-analysis of randomized trials.J Adv Nurs. 2018 Mar;74(3):501-506. doi: 10.1111/jan.13346. Epub 2017 Dec 18.
3	The Societal Cost of Schizophrenia: A Systematic Review.Pharmacoeconomics. 2017 Jan;35(1):25-42. doi: 10.1007/s40273-016-0444-6.
4	Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study.Am J Respir Crit Care Med. 2014 Feb 15;189(4):408-18. doi: 10.1164/rccm.201306-1061OC.
5	Genome-wide association identifies diverse causes of common variable immunodeficiency.J Allergy Clin Immunol. 2011 Jun;127(6):1360-7.e6. doi: 10.1016/j.jaci.2011.02.039. Epub 2011 Apr 17.
6	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.
7	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
8	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.
9	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10	Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
11	Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
12	Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
13	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.
14	Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
15	PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
16	Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
17	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
18	Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
19	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.