Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSEV0JU)

• DOT Name: ADP-ribosylation factor-binding protein GGA1 (GGA1)
• Synonyms: Gamma-adaptin-related protein 1; Golgi-localized, gamma ear-containing, ARF-binding protein 1
• Gene Name: GGA1
• UniProt ID: GGA1_HUMAN
• PDB ID: 1J2J; 1JWF; 1JWG; 1NA8; 1NAF; 1NWM; 1O3X; 1OM9; 1OXZ; 1PY1; 1UJJ; 1UJK; 1X79; 2DWX; 2DWY; 3G2S; 3G2T; 3G2U; 3G2V; 3G2W
• Pfam ID: PF02883 ; PF03127 ; PF18308 ; PF00790
• Sequence:
  MEPAMEPETLEARINRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQE
  WEAIQALTVLETCMKSCGKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLY
  SWTVGLPEEVKIAEAYQMLKKQGIVKSDPKLPDDTTFPLPPPRPKNVIFEDEEKSKMLAR
  LLKSSHPEDLRAANKLIKEMVQEDQKRMEKISKRVNAIEEVNNNVKLLTEMVMSHSQGGA
  AAGSSEDLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQVINLYKQLVRG
  EEVNGDATAGSIPGSTSALLDLSGLDLPPAGTTYPAMPTRPGEQASPEQPSASVSLLDDE
  LMSLGLSDPTPPSGPSLDGTGWNSFQSSDATEPPAPALAQAPSMESRPPAQTSLPASSGL
  DDLDLLGKTLLQQSLPPESQQVRWEKQQPTPRLTLRDLQNKSSSCSSPSSSATSLLHTVS
  PEPPRPPQQPVPTELSLASITVPLESIKPSNILPVTVYDQHGFRILFHFARDPLPGRSDV
  LVVVVSMLSTAPQPIRNIVFQSAVPKVMKVKLQPPSGTELPAFNPIVHPSAITQVLLLAN
  PQKEKVRLRYKLTFTMGDQTYNEMGDVDQFPPPETWGSL
• Function: Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif. Mediates export of the GPCR receptor ADRA2B to the cell surface. Required for targeting PKD1:PKD2 complex from the trans-Golgi network to the cilium membrane. Regulates retrograde transport of proteins such as phosphorylated form of BACE1 from endosomes to the trans-Golgi network.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Lysosome (hsa04142)
• Reactome Pathway:
  Amyloid fiber formation (R-HSA-977225)
  TBC/RABGAPs (R-HSA-8854214)

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADP-ribosylation factor-binding protein GGA1 (GGA1).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ADP-ribosylation factor-binding protein GGA1 (GGA1).	[3]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of ADP-ribosylation factor-binding protein GGA1 (GGA1).	[4]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of ADP-ribosylation factor-binding protein GGA1 (GGA1).	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of ADP-ribosylation factor-binding protein GGA1 (GGA1).	[2]

References

• [1] 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.
• [2] 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.
• [3] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [4] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [5] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.