Details of Drug Off-Target (DOT)

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

DOT Name	CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4)
Synonyms	Alpha 2,3-ST 4; Beta-galactoside alpha-2,3-sialyltransferase 4; EC 2.4.3.2; EC 2.4.3.4; Alpha 2,3-sialyltransferase IV; Gal-NAc6S; Gal-beta-1,3-GalNAc-alpha-2,3-sialyltransferase; Gal-beta-1,4-GlcNAc-alpha-2,3-sialyltransferase; N-acetyllactosaminide alpha-2,3-sialyltransferase; EC 2.4.3.6; SAT-3; ST-4; ST3Gal IV; ST3GalIV; ST3GalA.2; STZ; Sialyltransferase 4C; SIAT4-C
Gene Name	ST3GAL4
Related Disease	Cerebral infarction ( ) Type-1 diabetes ( ) Acute myelogenous leukaemia ( ) Advanced cancer ( ) Alzheimer disease ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Cataract ( ) Clear cell renal carcinoma ( ) Colon carcinoma ( ) Depression ( ) Diabetic kidney disease ( ) Diabetic neuropathy ( ) Dilated cardiomyopathy 1A ( ) Enterovirus infection ( ) Hepatocellular carcinoma ( ) High blood pressure ( ) Hyperglycemia ( ) Hyperinsulinemia ( ) Intellectual disability, autosomal dominant 4 ( ) Melanoma ( ) Metabolic disorder ( ) Myocardial infarction ( ) Neuralgia ( ) Non-alcoholic fatty liver disease ( ) Non-insulin dependent diabetes ( ) Osteoporosis ( ) Pancreatic cancer ( ) Peripheral neuropathy ( ) Precancerous condition ( ) Renal cell carcinoma ( ) Retinopathy ( ) Type-1/2 diabetes ( ) Venous thromboembolism ( ) Cervical cancer ( ) Cervical carcinoma ( ) Coronary heart disease ( ) Neoplasm ( ) Hyperlipidemia ( ) Alopecia ( ) Cardiomyopathy ( ) Colorectal carcinoma ( ) Dementia ( ) Nervous system inflammation ( ) Non-alcoholic steatohepatitis ( ) Squamous cell carcinoma ( )
UniProt ID	SIA4C_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.4.3.2; 2.4.3.4; 2.4.3.6
Pfam ID	PF00777
Sequence	MVSKSRWKLLAMLALVLVVMVWYSISREDRYIELFYFPIPEKKEPCLQGEAESKASKLFG NYSRDQPIFLRLEDYFWVKTPSAYELPYGTKGSEDLLLRVLAITSSSIPKNIQSLRCRRC VVVGNGHRLRNSSLGDAINKYDVVIRLNNAPVAGYEGDVGSKTTMRLFYPESAHFDPKVE NNPDTLLVLVAFKAMDFHWIETILSDKKRVRKGFWKQPPLIWDVNPKQIRILNPFFMEIA ADKLLSLPMQQPRKIKQKPTTGLLAITLALHLCDLVHIAGFGYPDAYNKKQTIHYYEQIT LKSMAGSGHNVSQEALAIKRMLEMGAIKNLTSF
Function	A beta-galactoside alpha2-3 sialyltransferase involved in terminal sialylation of glycoproteins and glycolipids. Catalyzes the transfer of sialic acid (N-acetyl-neuraminic acid; Neu5Ac) from the nucleotide sugar donor CMP-Neu5Ac onto acceptor Galbeta-(1->3)-GalNAc- and Galbeta-(1->4)-GlcNAc-terminated glycoconjugates through an alpha2-3 linkage. Plays a major role in hemostasis. Responsible for sialylation of plasma VWF/von Willebrand factor, preventing its recognition by asialoglycoprotein receptors (ASGPR) and subsequent clearance. Regulates ASGPR-mediated clearance of platelets. Participates in the biosynthesis of the sialyl Lewis X epitopes, both on O- and N-glycans, which are recognized by SELE/E-selectin, SELP/P-selectin and SELL/L-selectin. Essential for selectin-mediated rolling and adhesion of leukocytes during extravasation. Contributes to adhesion and transendothelial migration of neutrophils likely through terminal sialylation of CXCR2. In glycosphingolipid biosynthesis, sialylates GM1 and GA1 gangliosides to form GD1a and GM1b, respectively. Metabolizes brain c-series ganglioside GT1c forming GQ1c. Synthesizes ganglioside LM1 (IV3Neu5Ac-nLc4Cer), a major structural component of peripheral nerve myelin.
Tissue Specificity	Highly expressed in adult placenta, heart and kidney.
KEGG Pathway	Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601 ) Metabolic pathways (hsa01100 )
Reactome Pathway	Keratan sulfate biosynthesis (R-HSA-2022854 ) Sialic acid metabolism (R-HSA-4085001 ) Lewis blood group biosynthesis (R-HSA-9037629 ) Maturation of protein 3a (R-HSA-9683673 ) Maturation of spike protein (R-HSA-9694548 ) Maturation of protein 3a (R-HSA-9694719 ) N-Glycan antennae elongation (R-HSA-975577 ) Termination of O-glycan biosynthesis (R-HSA-977068 ) Pre-NOTCH Processing in Golgi (R-HSA-1912420 )
BioCyc Pathway	MetaCyc:HS03285-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cerebral infarction	DISR1WNP	Definitive	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Cataract	DISUD7SL	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Depression	DIS3XJ69	Strong	Biomarker	[10]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[11]
Diabetic neuropathy	DISX6VF8	Strong	Biomarker	[12]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[13]
Enterovirus infection	DISH2UDP	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
High blood pressure	DISY2OHH	Strong	Biomarker	[16]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[17]
Hyperinsulinemia	DISIDWT6	Strong	Altered Expression	[18]
Intellectual disability, autosomal dominant 4	DISNHOJN	Strong	Genetic Variation	[19]
Melanoma	DIS1RRCY	Strong	Biomarker	[9]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[11]
Myocardial infarction	DIS655KI	Strong	Biomarker	[20]
Neuralgia	DISWO58J	Strong	Biomarker	[21]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[22]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[23]
Osteoporosis	DISF2JE0	Strong	Biomarker	[24]
Pancreatic cancer	DISJC981	Strong	Biomarker	[25]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[26]
Precancerous condition	DISV06FL	Strong	Altered Expression	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[8]
Retinopathy	DISB4B0F	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[13]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[28]
Cervical cancer	DISFSHPF	moderate	Altered Expression	[4]
Cervical carcinoma	DIST4S00	moderate	Altered Expression	[4]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[29]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Hyperlipidemia	DIS61J3S	Disputed	Altered Expression	[30]
Alopecia	DIS37HU4	Limited	Genetic Variation	[31]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[32]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[33]
Dementia	DISXL1WY	Limited	Biomarker	[34]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[35]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[36]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[37]
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⏷ Show the Full List of 46 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

7 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 CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[43]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[45]
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⏷ Show the Full List of 7 Drug(s)

2 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 CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[44]
	DM9CEI5		increases the phosphorylation of CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 (ST3GAL4).	[46]
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References

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