Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB0TKAG)

• DOT Name: Beta-galactosidase (GLB1)
• Synonyms: EC 3.2.1.23; Acid beta-galactosidase; Lactase; Elastin receptor 1
• Gene Name: GLB1
• Related Disease:
  GM1 gangliosidosis
  GM1 gangliosidosis type 3
  Mucopolysaccharidosis type 4B
  GM1 gangliosidosis type 1
  GM1 gangliosidosis type 2
• UniProt ID: BGAL_HUMAN
• PDB ID: 3THC; 3THD; 3WEZ; 3WF0; 3WF1; 3WF2; 3WF3; 3WF4
• EC Number: 3.2.1.23
• Pfam ID: PF21317 ; PF21467 ; PF01301
• Sequence:
  MPGFLVRILPLLLVLLLLGPTRGLRNATQRMFEIDYSRDSFLKDGQPFRYISGSIHYSRV
  PRFYWKDRLLKMKMAGLNAIQTYVPWNFHEPWPGQYQFSEDHDVEYFLRLAHELGLLVIL
  RPGPYICAEWEMGGLPAWLLEKESILLRSSDPDYLAAVDKWLGVLLPKMKPLLYQNGGPV
  ITVQVENEYGSYFACDFDYLRFLQKRFRHHLGDDVVLFTTDGAHKTFLKCGALQGLYTTV
  DFGTGSNITDAFLSQRKCEPKGPLINSEFYTGWLDHWGQPHSTIKTEAVASSLYDILARG
  ASVNLYMFIGGTNFAYWNGANSPYAAQPTSYDYDAPLSEAGDLTEKYFALRNIIQKFEKV
  PEGPIPPSTPKFAYGKVTLEKLKTVGAALDILCPSGPIKSLYPLTFIQVKQHYGFVLYRT
  TLPQDCSNPAPLSSPLNGVHDRAYVAVDGIPQGVLERNNVITLNITGKAGATLDLLVENM
  GRVNYGAYINDFKGLVSNLTLSSNILTDWTIFPLDTEDAVRSHLGGWGHRDSGHHDEAWA
  HNSSNYTLPAFYMGNFSIPSGIPDLPQDTFIQFPGWTKGQVWINGFNLGRYWPARGPQLT
  LFVPQHILMTSAPNTITVLELEWAPCSSDDPELCAVTFVDRPVIGSSVTYDHPSKPVEKR
  LMPPPPQKNKDSWLDHV
• Function: [Isoform 1]: Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans; [Isoform 2]: Has no beta-galactosidase catalytic activity, but plays functional roles in the formation of extracellular elastic fibers (elastogenesis) and in the development of connective tissue. Seems to be identical to the elastin-binding protein (EBP), a major component of the non-integrin cell surface receptor expressed on fibroblasts, smooth muscle cells, chondroblasts, leukocytes, and certain cancer cell types. In elastin producing cells, associates with tropoelastin intracellularly and functions as a recycling molecular chaperone which facilitates the secretions of tropoelastin and its assembly into elastic fibers.
• Tissue Specificity: Detected in placenta (at protein level) . Detected in fibroblasts and testis .
• KEGG Pathway:
  Galactose metabolism (hsa00052)
  Other glycan degradation (hsa00511)
  Glycosaminoglycan degradation (hsa00531)
  Sphingolipid metabolism (hsa00600)
  Glycosphingolipid biosynthesis - ganglio series (hsa00604)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)
• Reactome Pathway:
  HS-GAG degradation (R-HSA-2024096)
  MPS IV - Morquio syndrome B (R-HSA-2206308)
  Sialic acid metabolism (R-HSA-4085001)
  Defective NEU1 causes sialidosis (R-HSA-4341670)
  Neutrophil degranulation (R-HSA-6798695)
  Glycosphingolipid catabolism (R-HSA-9840310)
  Keratan sulfate degradation (R-HSA-2022857)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
GM1 gangliosidosis	DISN3L2M	Definitive	Autosomal recessive	[1]
GM1 gangliosidosis type 3	DISS3EX6	Definitive	Autosomal recessive	[2]
Mucopolysaccharidosis type 4B	DISPCAUH	Definitive	Autosomal recessive	[1]
GM1 gangliosidosis type 1	DISE7GM9	Strong	Autosomal recessive	[3]
GM1 gangliosidosis type 2	DISYMW73	Strong	Autosomal recessive	[3]

27 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 Beta-galactosidase (GLB1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Beta-galactosidase (GLB1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Beta-galactosidase (GLB1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Beta-galactosidase (GLB1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-galactosidase (GLB1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Beta-galactosidase (GLB1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Beta-galactosidase (GLB1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Beta-galactosidase (GLB1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the activity of Beta-galactosidase (GLB1).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Beta-galactosidase (GLB1).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Beta-galactosidase (GLB1).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Beta-galactosidase (GLB1).	[15]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the activity of Beta-galactosidase (GLB1).	[16]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the activity of Beta-galactosidase (GLB1).	[17]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Beta-galactosidase (GLB1).	[9]
Ritonavir	DMU764S	Approved	Ritonavir increases the activity of Beta-galactosidase (GLB1).	[18]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide decreases the activity of Beta-galactosidase (GLB1).	[10]
Bendamustine hydrochloride	DMFH15Z	Approved	Bendamustine hydrochloride increases the expression of Beta-galactosidase (GLB1).	[9]
BMS-777607	DMGM7QD	Phase 1/2	BMS-777607 increases the activity of Beta-galactosidase (GLB1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Beta-galactosidase (GLB1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Beta-galactosidase (GLB1).	[21]
D-glucose	DMMG2TO	Investigative	D-glucose increases the activity of Beta-galactosidase (GLB1).	[22]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the activity of Beta-galactosidase (GLB1).	[17]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the activity of Beta-galactosidase (GLB1).	[23]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Beta-galactosidase (GLB1).	[24]
Wogonin	DMGCF51	Investigative	Wogonin increases the expression of Beta-galactosidase (GLB1).	[25]
	DMQNVR8		increases the activity of Beta-galactosidase (GLB1).	[18]

References

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