Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9MXA2J)

• DOT Name: Secretory carrier-associated membrane protein 5 (SCAMP5)
• Synonyms: Secretory carrier membrane protein 5; hSCAMP5
• Gene Name: SCAMP5
• Related Disease:
  Autism
  Huntington disease
  Complex neurodevelopmental disorder
  Intellectual disability
  Epilepsy
  Neurodevelopmental disorder
  Systemic lupus erythematosus
• UniProt ID: SCAM5_HUMAN
• Pfam ID: PF04144
• Sequence:
  MAEKVNNFPPLPKFIPLKPCFYQDFEADIPPQHVSMTKRLYYLWMLNSVTLAVNLVGCLA
  WLIGGGGATNFGLAFLWLILFTPCSYVCWFRPIYKAFKTDSSFSFMAFFFTFMAQLVISI
  IQAVGIPGWGVCGWIATISFFGTNIGSAVVMLIPTVMFTVMAVFSFIALSMVHKFYRGSG
  GSFSKAQEEWTTGAWKNPHVQQAAQNAAMGAAQGAMNQPQTQYSATPNYTYSNEM
• Function: Required for the calcium-dependent exocytosis of signal sequence-containing cytokines such as CCL5. Probably acts in cooperation with the SNARE machinery. May play a role in accumulation of expanded polyglutamine (polyQ) protein huntingtin (HTT) in case of endoplasmic reticulum stress by inhibiting the endocytosis pathway.
• Tissue Specificity: Expressed both by neuronal and non-neuronal tissues. Expressed in brain, stomach, thyroid, spinal cord, lymph node, trachea, adrenal gland, bone marrow and in the different parts of brain. In thyroid tissues, it is expressed by the follicular epithelial cells. In the adrenal gland tissues it is detected in the zona fasciculata of the cortex region (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Altered Expression	[1]
Huntington disease	DISQPLA4	Strong	Biomarker	[2]
Complex neurodevelopmental disorder	DISB9AFI	Moderate	Autosomal dominant	[3]
Intellectual disability	DISMBNXP	moderate	Biomarker	[4]
Epilepsy	DISBB28L	Limited	Autosomal recessive	[5]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[4]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[6]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Secretory carrier-associated membrane protein 5 (SCAMP5) affects the response to substance of Temozolomide.	[17]
DTI-015	DMXZRW0	Approved	Secretory carrier-associated membrane protein 5 (SCAMP5) affects the response to substance of DTI-015.	[17]

3 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 Secretory carrier-associated membrane protein 5 (SCAMP5).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Secretory carrier-associated membrane protein 5 (SCAMP5).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Secretory carrier-associated membrane protein 5 (SCAMP5).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Secretory carrier-associated membrane protein 5 (SCAMP5).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Secretory carrier-associated membrane protein 5 (SCAMP5).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Secretory carrier-associated membrane protein 5 (SCAMP5).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Secretory carrier-associated membrane protein 5 (SCAMP5).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Secretory carrier-associated membrane protein 5 (SCAMP5).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Secretory carrier-associated membrane protein 5 (SCAMP5).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Secretory carrier-associated membrane protein 5 (SCAMP5).	[16]

References

• [1] Impairment of Release Site Clearance within the Active Zone by Reduced SCAMP5 Expression Causes Short-Term Depression of Synaptic Release.Cell Rep. 2018 Mar 20;22(12):3339-3350. doi: 10.1016/j.celrep.2018.02.088.
• [2] Secretory carrier membrane protein 5 is an autophagy inhibitor that promotes the secretion of -synuclein via exosome.PLoS One. 2017 Jul 11;12(7):e0180892. doi: 10.1371/journal.pone.0180892. eCollection 2017.
• [3] Novel SCAMPs lacking NPF repeats: ubiquitous and synaptic vesicle-specific forms implicate SCAMPs in multiple membrane-trafficking functions. J Neurosci. 2000 Nov 1;20(21):7941-50. doi: 10.1523/JNEUROSCI.20-21-07941.2000.
• [4] De novo SCAMP5 mutation causes a neurodevelopmental disorder with autistic features and seizures.J Med Genet. 2020 Feb;57(2):138-144. doi: 10.1136/jmedgenet-2018-105927. Epub 2019 Aug 22.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus.Nat Genet. 2016 Aug;48(8):940-946. doi: 10.1038/ng.3603. Epub 2016 Jul 11.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [17] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.