Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2SWBT6)

DOT Name Chemokine-like protein TAFA-5 (TAFA5)
Gene Name TAFA5
Related Disease
Advanced cancer ( )
Gastric cancer ( )
Metabolic disorder ( )
Neoplasm ( )
Neuromyelitis optica ( )
Non-insulin dependent diabetes ( )
Pancreatic cancer ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
Adenovirus infection ( )
Obesity ( )
UniProt ID
TAFA5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12020
Sequence
MAPSPRTGSRQDATALPSMSSTFWAFMILASLLIAYCSQLAAGTCEIVTLDRDSSQPRRT
IARQTARCACRKGQIAGTTRARPACVDARIIKTKQWCDMLPCLEGEGCDLLINRSGWTCT
QPGGRIKTTTVS
Function
Acts as a chemokine-like protein by regulating cell proliferation and migration through activation of G protein-coupled receptors (GPCRs), such as S1PR2 and FPR2. Stimulates chemotactic migration of macrophages mediated by the MAPK3/ERK1 and AKT1 pathway. Blocks TNFSF11/RANKL-induced osteoclast formation from macrophages by inhibiting up-regulation of osteoclast fusogenic and differentiation genes. Stimulation of macrophage migration and inhibition of osteoclast formation is mediated via GPCR FPR2. Acts as an adipokine by negatively regulating vascular smooth muscle cell (VSMC) proliferation and migration in response to platelet-derived growth factor stimulation via GPCR S1PR2 and G protein GNA12/GNA13-transmitted RHOA signaling. Inhibits injury-induced cell proliferation and neointima formation in the femoral arteries.
Tissue Specificity Expressed in the subcutaneous and perirenal adipose tissue (at protein level) . Highly expressed in adipose tissue with moderate expression in the brain and ovary . Isoform 2: Brain-specific .

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Gastric cancer DISXGOUK Strong Biomarker [1]
Metabolic disorder DIS71G5H Strong Biomarker [2]
Neoplasm DISZKGEW Strong Altered Expression [1]
Neuromyelitis optica DISBFGKL Strong Biomarker [3]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [2]
Pancreatic cancer DISJC981 Strong Genetic Variation [4]
Stomach cancer DISKIJSX Strong Biomarker [1]
Type-1/2 diabetes DISIUHAP Strong Genetic Variation [2]
Adenovirus infection DISUYSBZ Limited Altered Expression [5]
Obesity DIS47Y1K Limited Altered Expression [5]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Chemokine-like protein TAFA-5 (TAFA5). [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Chemokine-like protein TAFA-5 (TAFA5). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Chemokine-like protein TAFA-5 (TAFA5). [15]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Chemokine-like protein TAFA-5 (TAFA5). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Chemokine-like protein TAFA-5 (TAFA5). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Chemokine-like protein TAFA-5 (TAFA5). [9]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Chemokine-like protein TAFA-5 (TAFA5). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Chemokine-like protein TAFA-5 (TAFA5). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Chemokine-like protein TAFA-5 (TAFA5). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Chemokine-like protein TAFA-5 (TAFA5). [14]
Resorcinol DMM37C0 Investigative Resorcinol increases the expression of Chemokine-like protein TAFA-5 (TAFA5). [16]
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⏷ Show the Full List of 8 Drug(s)

References

1 TAFA5 promotes proliferation and migration in gastric cancer.Mol Med Rep. 2019 Nov;20(5):4477-4488. doi: 10.3892/mmr.2019.10724. Epub 2019 Oct 2.
2 Association of serum FAM19A5 with metabolic and vascular risk factors in human subjects with or without type 2 diabetes.Diab Vasc Dis Res. 2019 Nov;16(6):530-538. doi: 10.1177/1479164119860746. Epub 2019 Jul 8.
3 Serum FAM19A5 in neuromyelitis optica spectrum disorders: Can it be a new biomarker representing clinical status?.Mult Scler. 2020 Nov;26(13):1700-1707. doi: 10.1177/1352458519885489. Epub 2019 Nov 4.
4 Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations.Nat Genet. 2011 Dec 11;44(1):62-6. doi: 10.1038/ng.1020.
5 Novel Adipokine, FAM19A5, Inhibits Neointima Formation After Injury Through Sphingosine-1-Phosphate Receptor 2.Circulation. 2018 Jul 3;138(1):48-63. doi: 10.1161/CIRCULATIONAHA.117.032398. Epub 2018 Feb 16.
6 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.
7 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
11 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.
12 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
13 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
14 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
15 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.
16 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.