Details of Drug Off-Target (DOT)

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

• DOT Name: AP-5 complex subunit mu-1 (AP5M1)
• Synonyms: Adaptor-related protein complex 5 subunit mu-1; Mu5; Mu-2-related death-inducing protein; MuD; Putative HIV-1 infection-related protein
• Gene Name: AP5M1
• Related Disease:
  Acute myelogenous leukaemia
  Brain neoplasm
  Glioblastoma multiforme
  Neoplasm
  Acute leukaemia
  Astrocytoma
  Childhood myelodysplastic syndrome
  Chronic graft versus host disease
  Clear cell renal carcinoma
  Graft-versus-host disease
  Hemorrhoids
  Myelodysplastic syndrome
  Papillary renal cell carcinoma
  Renal cell carcinoma
  X-linked lymphoproliferative syndrome
  B-cell neoplasm
  Cervical carcinoma
  Kidney cancer
  Renal carcinoma
  Advanced cancer
• UniProt ID: AP5M1_HUMAN
• Pfam ID: PF00928
• Sequence:
  MAQRAVWLISHEPGTPLCGTVRFSRRYPTVEKRARVFNGASYVPVPEDGPFLKALLFELR
  LLDDDKDFVESRDSCSRINKTSIYGLLIGGEELWPVVAFLKNDMIYACVPLVEQTLSPRP
  PLISVSGVSQGFEFLFGIQDFLYSGQKNDSELNTKLSQLPDLLLQACPFGTLLDANLQNS
  LDNTNFASVTQPQKQPAWKTGTYKGKPQVSISITEKVKSMQYDKQGIADTWQVVGTVTCK
  CDLEGIMPNVTISLSLPTNGSPLQDILVHPCVTSLDSAILTSSSIDAMDDSAFSGPYKFP
  FTPPLESFNLCFYTSQVPVPPILGFYQMKEEEVQLRITINLKLHESVKNNFEFCEAHIPF
  YNRGPITHLEYKTSFGQLEVFREKSLLIWIIGQKFPKSMEISLSGTVTFGAKSHEKQPFD
  PICTGETAYLKLHFRILDYTLTGCYADQHSVQVFASGKPKISAHRKLISSDYYIWNSKAP
  APVTYGSLLL
• Function: As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport. According to PubMed:18395520, it may play a role in cell death.
• Tissue Specificity: Expressed in various tumor cell lines including Jurkat, Hep-G2 and HeLa.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Brain neoplasm	DISY3EKS	Definitive	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[2]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[3]
Astrocytoma	DISL3V18	Strong	Biomarker	[4]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Biomarker	[3]
Chronic graft versus host disease	DIS1MM9J	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[6]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[7]
Hemorrhoids	DISQ5G6G	Strong	Biomarker	[8]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[6]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[6]
X-linked lymphoproliferative syndrome	DISA7MJ4	Strong	Biomarker	[9]
B-cell neoplasm	DISVY326	moderate	Altered Expression	[10]
Cervical carcinoma	DIST4S00	moderate	Altered Expression	[10]
Kidney cancer	DISBIPKM	moderate	Altered Expression	[11]
Renal carcinoma	DISER9XT	moderate	Altered Expression	[11]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[12]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	AP-5 complex subunit mu-1 (AP5M1) affects the response to substance of Topotecan.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of AP-5 complex subunit mu-1 (AP5M1).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of AP-5 complex subunit mu-1 (AP5M1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of AP-5 complex subunit mu-1 (AP5M1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of AP-5 complex subunit mu-1 (AP5M1).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of AP-5 complex subunit mu-1 (AP5M1).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of AP-5 complex subunit mu-1 (AP5M1).	[18]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of AP-5 complex subunit mu-1 (AP5M1).	[19]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of AP-5 complex subunit mu-1 (AP5M1).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of AP-5 complex subunit mu-1 (AP5M1).	[21]

References

• [1] Refined graft-versus-host disease/relapse-free survival in transplant from HLA-identical related or unrelated donors in acute myeloid leukemia.Bone Marrow Transplant. 2018 Oct;53(10):1295-1303. doi: 10.1038/s41409-018-0169-6. Epub 2018 Apr 16.
• [2] MUDENG Expression Profiling in Cohorts and Brain Tumor Biospecimens to Evaluate Its Role in Cancer.Front Genet. 2019 Sep 19;10:884. doi: 10.3389/fgene.2019.00884. eCollection 2019.
• [3] Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study.Blood. 2012 Mar 8;119(10):2409-16. doi: 10.1182/blood-2011-08-372573. Epub 2011 Oct 31.
• [4] Silver nanoparticle-induced hormesis of astroglioma cells: A Mu-2-related death-inducing protein-orchestrated modus operandi.Int J Biol Macromol. 2018 Oct 1;117:1147-1156. doi: 10.1016/j.ijbiomac.2018.05.234. Epub 2018 Jun 2.
• [5] Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT.Leukemia. 2020 Jan;34(1):283-292. doi: 10.1038/s41375-019-0544-3. Epub 2019 Aug 19.
• [6] Integrated molecular analysis of clear-cell renal cell carcinoma.Nat Genet. 2013 Aug;45(8):860-7. doi: 10.1038/ng.2699. Epub 2013 Jun 24.
• [7] Influence of Donor Type (Sibling versus Matched Unrelated Donor versus Haploidentical Donor) on Outcomes after Clofarabine-Based Reduced-Intensity Conditioning Allograft for Myeloid Malignancies.Biol Blood Marrow Transplant. 2019 Jul;25(7):1465-1471. doi: 10.1016/j.bbmt.2019.03.025. Epub 2019 Mar 27.
• [8] Correction: Altered mental status and an acid-base disturbance.Cleve Clin J Med. 2017 Mar;84(3):214.
• [9] Matched unrelated allogeneic bone marrow transplantation for recurrent malignant lymphoma in a patient with X-linked lymphoproliferative disease (XLP).Bone Marrow Transplant. 1998 Sep;22(6):603-4. doi: 10.1038/sj.bmt.1701389.
• [10] BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells.Biochem Biophys Res Commun. 2019 Oct 15;518(2):368-373. doi: 10.1016/j.bbrc.2019.08.065. Epub 2019 Aug 16.
• [11] Landscape of cancer diagnostic biomarkers from specifically expressed genes.Brief Bioinform. 2020 Dec 1;21(6):2175-2184. doi: 10.1093/bib/bbz131.
• [12] Allogeneic stem cell transplantation for patients with relapsed or refractory T-cell lymphoma: efficacy of lymphoma-directed conditioning against advanced disease.Bone Marrow Transplant. 2019 Jun;54(6):877-884. doi: 10.1038/s41409-018-0360-9. Epub 2018 Nov 9.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [16] Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study. BMC Med Genomics. 2011 Mar 31;4:29. doi: 10.1186/1755-8794-4-29.
• [17] 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.
• [18] 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.
• [19] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [20] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [21] 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.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.