Details of Drug Off-Target (DOT)

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

• DOT Name: Golgin subfamily A member 4 (GOLGA4)
• Synonyms: 256 kDa golgin; Golgin-245; Protein 72.1; Trans-Golgi p230
• Gene Name: GOLGA4
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Cutaneous mastocytosis
  Cutaneous melanoma
  Fanconi anemia complementation group A
  Fanconi's anemia
  Isolated congenital microcephaly
  Melanoma
  Metastatic malignant neoplasm
  Metastatic melanoma
  Myocardial infarction
  Prostate cancer
  Prostate neoplasm
  Sjogren syndrome
  Skin disease
  Peritonsillar abscess
  Anencephaly
  Neural tube defect
  Arthritis
  Astrocytoma
  Coronary heart disease
  Glioblastoma multiforme
  Streptococcal B infection
• UniProt ID: GOGA4_HUMAN
• PDB ID: 1R4A; 1UPT
• Pfam ID: PF01465
• Sequence:
  MFKKLKQKISEEQQQLQQALAPAQASSNSSTPTRMRSRTSSFTEQLDEGTPNRESGDTQS
  FAQKLQLRVPSVESLFRSPIKESLFRSSSKESLVRTSSRESLNRLDLDSSTASFDPPSDM
  DSEAEDLVGNSDSLNKEQLIQRLRRMERSLSSYRGKYSELVTAYQMLQREKKKLQGILSQ
  SQDKSLRRIAELREELQMDQQAKKHLQEEFDASLEEKDQYISVLQTQVSLLKQRLRNGPM
  NVDVLKPLPQLEPQAEVFTKEENPESDGEPVVEDGTSVKTLETLQQRVKRQENLLKRCKE
  TIQSHKEQCTLLTSEKEALQEQLDERLQELEKIKDLHMAEKTKLITQLRDAKNLIEQLEQ
  DKGMVIAETKRQMHETLEMKEEEIAQLRSRIKQMTTQGEELREQKEKSERAAFEELEKAL
  STAQKTEEARRKLKAEMDEQIKTIEKTSEEERISLQQELSRVKQEVVDVMKKSSEEQIAK
  LQKLHEKELARKEQELTKKLQTREREFQEQMKVALEKSQSEYLKISQEKEQQESLALEEL
  ELQKKAILTESENKLRDLQQEAETYRTRILELESSLEKSLQENKNQSKDLAVHLEAEKNK
  HNKEITVMVEKHKTELESLKHQQDALWTEKLQVLKQQYQTEMEKLREKCEQEKETLLKDK
  EIIFQAHIEEMNEKTLEKLDVKQTELESLSSELSEVLKARHKLEEELSVLKDQTDKMKQE
  LEAKMDEQKNHHQQQVDSIIKEHEVSIQRTEKALKDQINQLELLLKERDKHLKEHQAHVE
  NLEADIKRSEGELQQASAKLDVFQSYQSATHEQTKAYEEQLAQLQQKLLDLETERILLTK
  QVAEVEAQKKDVCTELDAHKIQVQDLMQQLEKQNSEMEQKVKSLTQVYESKLEDGNKEQE
  QTKQILVEKENMILQMREGQKKEIEILTQKLSAKEDSIHILNEEYETKFKNQEKKMEKVK
  QKAKEMQETLKKKLLDQEAKLKKELENTALELSQKEKQFNAKMLEMAQANSAGISDAVSR
  LETNQKEQIESLTEVHRRELNDVISIWEKKLNQQAEELQEIHEIQLQEKEQEVAELKQKI
  LLFGCEKEEMNKEITWLKEEGVKQDTTLNELQEQLKQKSAHVNSLAQDETKLKAHLEKLE
  VDLNKSLKENTFLQEQLVELKMLAEEDKRKVSELTSKLKTTDEEFQSLKSSHEKSNKSLE
  DKSLEFKKLSEELAIQLDICCKKTEALLEAKTNELINISSSKTNAILSRISHCQHRTTKV
  KEALLIKTCTVSELEAQLRQLTEEQNTLNISFQQATHQLEEKENQIKSMKADIESLVTEK
  EALQKEGGNQQQAASEKESCITQLKKELSENINAVTLMKEELKEKKVEISSLSKQLTDLN
  VQLQNSISLSEKEAAISSLRKQYDEEKCELLDQVQDLSFKVDTLSKEKISALEQVDDWSN
  KFSEWKKKAQSRFTQHQNTVKELQIQLELKSKEAYEKDEQINLLKEELDQQNKRFDCLKG
  EMEDDKSKMEKKESNLETELKSQTARIMELEDHITQKTIEIESLNEVLKNYNQQKDIEHK
  ELVQKLQHFQELGEEKDNRVKEAEEKILTLENQVYSMKAELETKKKELEHVNLSVKSKEE
  ELKALEDRLESESAAKLAELKRKAEQKIAAIKKQLLSQMEEKEEQYKKGTESHLSELNTK
  LQEREREVHILEEKLKSVESSQSETLIVPRSAKNVAAYTEQEEADSQGCVQKTYEEKISV
  LQRNLTEKEKLLQRVGQEKEETVSSHFEMRCQYQERLIKLEHAEAKQHEDQSMIGHLQEE
  LEEKNKKYSLIVAQHVEKEGGKNNIQAKQNLENVFDDVQKTLQEKELTCQILEQKIKELD
  SCLVRQKEVHRVEMEELTSKYEKLQALQQMDGRNKPTELLEENTEEKSKSHLVQPKLLSN
  MEAQHNDLEFKLAGAEREKQKLGKEIVRLQKDLRMLRKEHQQELEILKKEYDQEREEKIK
  QEQEDLELKHNSTLKQLMREFNTQLAQKEQELEMTIKETINKAQEVEAELLESHQEETNQ
  LLKKIAEKDDDLKRTAKRYEEILDAREEEMTAKVRDLQTQLEELQKKYQQKLEQEENPGN
  DNVTIMELQTQLAQKTTLISDSKLKEQEFREQIHNLEDRLKKYEKNVYATTVGTPYKGGN
  LYHTDVSLFGEPTEFEYLRKVLFEYMMGRETKTMAKVITTVLKFPDDQTQKILEREDARL
  MFTSPRSGIF
• Function: Involved in vesicular trafficking at the Golgi apparatus level. May play a role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with MACF1. Involved in endosome-to-Golgi trafficking.
• Reactome Pathway:
  Signaling by membrane-tethered fusions of PDGFRA or PDGFRB (R-HSA-9673768)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Cutaneous mastocytosis	DISLBZEF	Strong	Biomarker	[4]
Cutaneous melanoma	DIS3MMH9	Strong	Genetic Variation	[5]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Altered Expression	[6]
Fanconi's anemia	DISGW6Q8	Strong	Altered Expression	[6]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[7]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[5]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[8]
Metastatic melanoma	DISSL43L	Strong	Genetic Variation	[5]
Myocardial infarction	DIS655KI	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[9]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[10]
Skin disease	DISDW8R6	Strong	Biomarker	[11]
Peritonsillar abscess	DISZZXTZ	moderate	Biomarker	[12]
Anencephaly	DISIYW6T	Disputed	Genetic Variation	[13]
Neural tube defect	DIS5J95E	Disputed	Genetic Variation	[13]
Arthritis	DIST1YEL	Limited	Biomarker	[14]
Astrocytoma	DISL3V18	Limited	Altered Expression	[1]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[15]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[1]
Streptococcal B infection	DISN80QT	Limited	Biomarker	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Golgin subfamily A member 4 (GOLGA4).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Golgin subfamily A member 4 (GOLGA4).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Golgin subfamily A member 4 (GOLGA4).	[19]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Golgin subfamily A member 4 (GOLGA4).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Golgin subfamily A member 4 (GOLGA4).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Golgin subfamily A member 4 (GOLGA4).	[22]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Golgin subfamily A member 4 (GOLGA4).	[23]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Golgin subfamily A member 4 (GOLGA4).	[24]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Golgin subfamily A member 4 (GOLGA4).	[25]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Golgin subfamily A member 4 (GOLGA4).	[26]
Tubocurarine	DMBZIVP	Approved	Tubocurarine decreases the expression of Golgin subfamily A member 4 (GOLGA4).	[24]
Mecamylamine	DMGQFYB	Approved	Mecamylamine increases the expression of Golgin subfamily A member 4 (GOLGA4).	[24]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Golgin subfamily A member 4 (GOLGA4).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Golgin subfamily A member 4 (GOLGA4).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Golgin subfamily A member 4 (GOLGA4).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Golgin subfamily A member 4 (GOLGA4).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Golgin subfamily A member 4 (GOLGA4).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Golgin subfamily A member 4 (GOLGA4).	[28]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Golgin subfamily A member 4 (GOLGA4).	[30]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Golgin subfamily A member 4 (GOLGA4).	[34]

References

• [1] Overexpression and Nucleolar Localization of -Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma.J Neuropathol Exp Neurol. 2015 Jul;74(7):723-42. doi: 10.1097/NEN.0000000000000212.
• [2] An interstitial deletion at 3p21.3 results in the genetic fusion of MLH1 and ITGA9 in a Lynch syndrome family.Clin Cancer Res. 2009 Feb 1;15(3):762-9. doi: 10.1158/1078-0432.CCR-08-1908.
• [3] Golgin A4 in CSF and granulovacuolar degenerations of patients with Alzheimer disease.Neurology. 2018 Nov 6;91(19):e1799-e1808. doi: 10.1212/WNL.0000000000006457. Epub 2018 Oct 10.
• [4] Mesenchymal stem cells overexpressing GCP-2 improve heart function through enhanced angiogenic properties in a myocardial infarction model.Cardiovasc Res. 2012 Sep 1;95(4):495-506. doi: 10.1093/cvr/cvs224. Epub 2012 Aug 10.
• [5] Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion.J Clin Invest. 2019 May 1;129(5):1940-1945. doi: 10.1172/JCI123089. Epub 2019 Mar 5.
• [6] Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex.J Biol Chem. 1999 Nov 12;274(46):32904-8. doi: 10.1074/jbc.274.46.32904.
• [7] Bi-allelic Pathogenic Variants in TUBGCP2 Cause Microcephaly and Lissencephaly Spectrum Disorders. Am J Hum Genet. 2019 Nov 7;105(5):1005-1015. doi: 10.1016/j.ajhg.2019.09.017. Epub 2019 Oct 17.
• [8] Isotypic neutralizing antibodies against mouse GCP-2/CXCL6 inhibit melanoma growth and metastasis.Cancer Lett. 2011 Mar 1;302(1):54-62. doi: 10.1016/j.canlet.2010.12.013. Epub 2011 Jan 13.
• [9] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [10] Novel variant of p230 trans-Golgi network protein identified by serum from Sjgren's syndrome patient.Eur J Cell Biol. 2000 Nov;79(11):790-4. doi: 10.1078/0171-9335-00114.
• [11] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [12] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
• [13] Role of parental folate pathway single nucleotide polymorphisms in altering the susceptibility to neural tube defects in South India.J Perinat Med. 2010;38(1):63-9. doi: 10.1515/jpm.2009.119.
• [14] Murine CXCR1 is a functional receptor for GCP-2/CXCL6 and interleukin-8/CXCL8.J Biol Chem. 2007 Apr 20;282(16):11658-66. doi: 10.1074/jbc.M607705200. Epub 2006 Dec 29.
• [15] Genetic and environmental influences on total plasma homocysteine and coronary artery disease (CAD) risk among South Indians.Clin Chim Acta. 2009 Jul;405(1-2):127-31. doi: 10.1016/j.cca.2009.04.015. Epub 2009 Apr 24.
• [16] Decidualization Mediated by Steroid Hormones Modulates the Innate Immunity in Response to Group B Streptococcal Infection in vitro.Gynecol Obstet Invest. 2017;82(6):592-600. doi: 10.1159/000454770. Epub 2017 Feb 2.
• [17] 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.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [20] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [21] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [22] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [23] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [24] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [25] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [26] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [27] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [28] 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.
• [29] 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.
• [30] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [31] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [32] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [33] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [34] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.