Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6WKC13)

DOT Name Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4)
Synonyms EC 2.4.1.41; Polypeptide GalNAc transferase 4; GalNAc-T4; pp-GaNTase 4; Protein-UDP acetylgalactosaminyltransferase 4; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 4
Gene Name GALNT4
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Cardiovascular disease ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Hepatocellular carcinoma ( )
UniProt ID
GALT4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5NQA; 6H0B
EC Number
2.4.1.41
Pfam ID
PF00535 ; PF00652
Sequence
MAVRWTWAGKSCLLLAFLTVAYIFVELLVSTFHASAGAGRARELGSRRLSDLQKNTEDLS
RPLYKKPPADSRALGEWGKASKLQLNEDELKQQEELIERYAINIYLSDRISLHRHIEDKR
MYECKSQKFNYRTLPTTSVIIAFYNEAWSTLLRTIHSVLETSPAVLLKEIILVDDLSDRV
YLKTQLETYISNLDRVRLIRTNKREGLVRARLIGATFATGDVLTFLDCHCECNSGWLEPL
LERIGRDETAVVCPVIDTIDWNTFEFYMQIGEPMIGGFDWRLTFQWHSVPKQERDRRISR
IDPIRSPTMAGGLFAVSKKYFQYLGTYDTGMEVWGGENLELSFRVWQCGGKLEIHPCSHV
GHVFPKRAPYARPNFLQNTARAAEVWMDEYKEHFYNRNPPARKEAYGDISERKLLRERLR
CKSFDWYLKNVFPNLHVPEDRPGWHGAIRSRGISSECLDYNSPDNNPTGANLSLFGCHGQ
GGNQFFEYTSNKEIRFNSVTELCAEVPEQKNYVGMQNCPKDGFPVPANIIWHFKEDGTIF
HPHSGLCLSAYRTPEGRPDVQMRTCDALDKNQIWSFEK
Function
Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a highest activity toward Muc7, EA2 and Muc2, with a lowest activity than GALNT2. Glycosylates 'Thr-57' of SELPLG.
Tissue Specificity Ubiquitous. Highly expressed in mucous cells.
KEGG Pathway
Mucin type O-glycan biosynthesis (hsa00512 )
Other types of O-glycan biosynthesis (hsa00514 )
Metabolic pathways (hsa01100 )
Reactome Pathway
O-linked glycosylation of mucins (R-HSA-913709 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [2]
Colon cancer DISVC52G Strong Biomarker [3]
Colon carcinoma DISJYKUO Strong Biomarker [3]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [4]
Coronary atherosclerosis DISKNDYU Strong Genetic Variation [2]
Coronary heart disease DIS5OIP1 Strong Genetic Variation [2]
Neoplasm DISZKGEW Strong Altered Expression [5]
Prostate cancer DISF190Y Strong Altered Expression [5]
Prostate carcinoma DISMJPLE Strong Altered Expression [5]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [6]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [7]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [9]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [10]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the expression of Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [11]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [12]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [11]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4). [13]
------------------------------------------------------------------------------------

References

1 Overexpression of microRNA-365 inhibits breast cancer cell growth and chemo-resistance through GALNT4.Eur Rev Med Pharmacol Sci. 2016 Nov;20(22):4710-4718.
2 Genetic polymorphisms in platelet-related proteins and coronary artery disease: investigation of candidate genes, including N-acetylgalactosaminyltransferase 4 (GALNT4) and sulphotransferase 1A1/2 (SULT1A1/2).J Thromb Thrombolysis. 2009 Feb;27(2):175-84. doi: 10.1007/s11239-008-0196-z. Epub 2008 Feb 8.
3 MiR-4262 promotes cell apoptosis and inhibits proliferation of colon cancer cells: involvement of GALNT4.Am J Transl Res. 2018 Dec 15;10(12):3969-3977. eCollection 2018.
4 The polypeptide N-acetylgalactosaminyltransferase 4 exhibits stage-dependent expression in colorectal cancer and affects tumorigenesis, invasion and differentiation.FEBS J. 2018 Aug;285(16):3041-3055. doi: 10.1111/febs.14593. Epub 2018 Jul 7.
5 MiR-506-3p acts as a novel tumor suppressor in prostate cancer through targeting GALNT4.Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5133-5138. doi: 10.26355/eurrev_201906_18177.
6 Loss of N-Acetylgalactosaminyltransferase-4 Orchestrates Oncogenic MicroRNA-9 in Hepatocellular Carcinoma.J Biol Chem. 2017 Feb 24;292(8):3186-3200. doi: 10.1074/jbc.M116.751685. Epub 2017 Jan 6.
7 A comparative transcriptomic study on the effects of valproic acid on two different hESCs lines in a neural teratogenicity test system. Toxicol Lett. 2014 Nov 18;231(1):38-44.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
10 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
11 Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.