Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7BFBLP)

• DOT Name: AP-3 complex subunit beta-2 (AP3B2)
• Synonyms: Adaptor protein complex AP-3 subunit beta-2; Adaptor-related protein complex 3 subunit beta-2; Beta-3B-adaptin; Clathrin assembly protein complex 3 beta-2 large chain; Neuron-specific vesicle coat protein beta-NAP
• Gene Name: AP3B2
• Related Disease:
  Developmental and epileptic encephalopathy, 48
  Autoimmune disease
  Sensory ataxia
  Undetermined early-onset epileptic encephalopathy
  Cognitive impairment
• UniProt ID: AP3B2_HUMAN
• Pfam ID: PF01602 ; PF14796
• Sequence:
  MSAAPAYSEDKGGSAGPGEPEYGHDPASGGIFSSDYKRHDDLKEMLDTNKDSLKLEAMKR
  IVAMIARGKNASDLFPAVVKNVACKNIEVKKLVYVYLVRYAEEQQDLALLSISTFQRGLK
  DPNQLIRASALRVLSSIRVPIIVPIMMLAIKEAASDMSPYVRKTAAHAIPKLYSLDSDQK
  DQLIEVIEKLLADKTTLVAGSVVMAFEEVCPERIDLIHKNYRKLCNLLIDVEEWGQVVII
  SMLTRYARTQFLSPTQNESLLEENAEKAFYGSEEDEAKGAGSEETAAAAAPSRKPYVMDP
  DHRLLLRNTKPLLQSRSAAVVMAVAQLYFHLAPKAEVGVIAKALVRLLRSHSEVQYVVLQ
  NVATMSIKRRGMFEPYLKSFYIRSTDPTQIKILKLEVLTNLANETNIPTVLREFQTYIRS
  MDKDFVAATIQAIGRCATNIGRVRDTCLNGLVQLLSNRDELVVAESVVVIKKLLQMQPAQ
  HGEIIKHLAKLTDNIQVPMARASILWLIGEYCEHVPRIAPDVLRKMAKSFTAEEDIVKLQ
  VINLAAKLYLTNSKQTKLLTQYVLSLAKYDQNYDIRDRARFTRQLIVPSEQGGALSRHAK
  KLFLAPKPAPVLESSFKDRDHFQLGSLSHLLNAKATGYQELPDWPEEAPDPSVRNVEVPE
  WTKCSNREKRKEKEKPFYSDSEGESGPTESADSDPESESESDSKSSSESGSGESSSESDN
  EDQDEDEEKGRGSESEQSEEDGKRKTKKKVPERKGEASSSDEGSDSSSSSSESEMTSESE
  EEQLEPASWSRKTPPSSKSAPATKEISLLDLEDFTPPSVQPVSPPAIVSTSLAADLEGLT
  LTDSTLVPSLLSPVSGVGRQELLHRVAGEGLAVDYTFSRQPFSGDPHMVSVHIHFSNSSD
  TPIKGLHVGTPKLPAGISIQEFPEIESLAPGESATAVMGINFCDSTQAANFQLCTQTRQF
  YVSIQPPVGELMAPVFMSENEFKKEQGKLMGMNEITEKLMLPDTCRSDHIVVQKVTATAN
  LGRVPCGTSDEYRFAGRTLTGGSLVLLTLDARPAGAAQLTVNSEKMVIGTMLVKDVIQAL
  TQ
• Function: Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. AP-3 appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.
• Tissue Specificity: Isoform 1 expression is specific to nervous system. Expressed in nerve terminal and cell body, and is associated with nerve-terminal vesicles. Expression seen in Purkinje cells, cortical neurons, neuroectodermal tumors and graded in cerebral cortex (deeper layers exhibit stronger expression) . Isoform 2 is expressed at high levels in brain and testis .
• KEGG Pathway: Lysosome (hsa04142)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental and epileptic encephalopathy, 48	DISSI159	Strong	Autosomal recessive	[1]
Autoimmune disease	DISORMTM	moderate	Biomarker	[2]
Sensory ataxia	DISSMCYQ	moderate	Biomarker	[2]
Undetermined early-onset epileptic encephalopathy	DISISEI2	Supportive	Autosomal dominant	[3]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of AP-3 complex subunit beta-2 (AP3B2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of AP-3 complex subunit beta-2 (AP3B2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of AP-3 complex subunit beta-2 (AP3B2).	[7]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of AP-3 complex subunit beta-2 (AP3B2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of AP-3 complex subunit beta-2 (AP3B2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of AP-3 complex subunit beta-2 (AP3B2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of AP-3 complex subunit beta-2 (AP3B2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of AP-3 complex subunit beta-2 (AP3B2).	[12]
Manganese	DMKT129	Investigative	Manganese increases the expression of AP-3 complex subunit beta-2 (AP3B2).	[13]

References

• [1] Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. Mol Psychiatry. 2017 Apr;22(4):615-624. doi: 10.1038/mp.2016.113. Epub 2016 Jul 19.
• [2] Autoimmune gait disturbance accompanying adaptor protein-3B2-IgG.Neurology. 2019 Sep 3;93(10):e954-e963. doi: 10.1212/WNL.0000000000008061. Epub 2019 Aug 1.
• [3] Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy. Am J Hum Genet. 2016 Dec 1;99(6):1368-1376. doi: 10.1016/j.ajhg.2016.10.009. Epub 2016 Nov 23.
• [4] Recurrent microdeletions of 15q25.2 are associated with increased risk of congenital diaphragmatic hernia, cognitive deficits and possibly Diamond--Blackfan anaemia.J Med Genet. 2010 Nov;47(11):777-81. doi: 10.1136/jmg.2009.075903. Epub 2010 Oct 4.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.