Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4U7SBG)

• DOT Name: Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1)
• Synonyms: Early estrogen-regulated protein; GABA(A) receptor-associated protein-like 1; Glandular epithelial cell protein 1; GEC-1
• Gene Name: GABARAPL1
• Related Disease:
  Early-onset anterior polar cataract
  Advanced cancer
  Autosomal dominant optic atrophy, classic form
  Breast adenocarcinoma
  Breast carcinoma
  Breast neoplasm
  Diamond-Blackfan anemia
  Diamond-Blackfan anemia 1
  Gastric cancer
  Hepatocellular carcinoma
  Neoplasm
  Poikiloderma with neutropenia
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Triple negative breast cancer
  Breast cancer
  Kidney cancer
  Lung cancer
  Renal carcinoma
• UniProt ID: GBRL1_HUMAN
• PDB ID: 2L8J; 2R2Q; 5DPT; 5LXH; 5LXI; 6HOI; 6HOL; 6YOO; 7AA7; 7AA9; 7JHX
• Pfam ID: PF02991
• Sequence:
  MKFQYKEDHPFEYRKKEGEKIRKKYPDRVPVIVEKAPKARVPDLDKRKYLVPSDLTVGQF
  YFLIRKRIHLRPEDALFFFVNNTIPPTSATMGQLYEDNHEEDYFLYVAYSDESVYGK
• Function: Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles. While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover.
• Tissue Specificity: Ubiquitous. Expressed at very high levels in the brain, heart, peripheral blood leukocytes, liver, kidney, placenta and skeletal muscle. Expressed at very low levels in thymus and small intestine. In the brain, expression is particularly intense in motoneurons in the embryo and in neurons involved in somatomotor and neuroendocrine functions in the adult, particularly in the substantia nigra pars compacta.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  Autophagy - other (hsa04136)
  Mitophagy - animal (hsa04137)
  Autophagy - animal (hsa04140)
  NOD-like receptor sig.ling pathway (hsa04621)
  GABAergic sy.pse (hsa04727)
• Reactome Pathway: Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Early-onset anterior polar cataract	DISTOPIY	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Biomarker	[2]
Breast adenocarcinoma	DISMPHJ0	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Diamond-Blackfan anemia	DISI2SNW	Strong	Biomarker	[5]
Diamond-Blackfan anemia 1	DISP4NUV	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Poikiloderma with neutropenia	DIS20E3L	Strong	Altered Expression	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	moderate	Biomarker	[4]
Kidney cancer	DISBIPKM	Disputed	Altered Expression	[10]
Lung cancer	DISCM4YA	Disputed	Altered Expression	[10]
Renal carcinoma	DISER9XT	Disputed	Altered Expression	[10]

26 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 Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[16]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[20]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[21]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[22]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[23]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[24]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[25]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[16]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[16]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[16]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[27]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[12]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[30]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[31]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1).	[32]

References

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