Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA7VHNE)

• DOT Name: Fc receptor-like protein 5 (FCRL5)
• Synonyms: FcR-like protein 5; FcRL5; BXMAS1; Fc receptor homolog 5; FcRH5; Immune receptor translocation-associated protein 2; CD antigen CD307e
• Gene Name: FCRL5
• Related Disease:
  Advanced cancer
  Allergic rhinitis
  Asthma
  Plasma cell myeloma
  Small lymphocytic lymphoma
  Adult lymphoma
  Ankylosing spondylitis
  B-cell neoplasm
  Burkitt lymphoma
  Hairy cell leukaemia
  Lymphoma
  Pediatric lymphoma
• UniProt ID: FCRL5_HUMAN
• Pfam ID: PF13895
• Sequence:
  MLLWVILLVLAPVSGQFARTPRPIIFLQPPWTTVFQGERVTLTCKGFRFYSPQKTKWYHR
  YLGKEILRETPDNILEVQESGEYRCQAQGSPLSSPVHLDFSSASLILQAPLSVFEGDSVV
  LRCRAKAEVTLNNTIYKNDNVLAFLNKRTDFHIPHACLKDNGAYRCTGYKESCCPVSSNT
  VKIQVQEPFTRPVLRASSFQPISGNPVTLTCETQLSLERSDVPLRFRFFRDDQTLGLGWS
  LSPNFQITAMWSKDSGFYWCKAATMPYSVISDSPRSWIQVQIPASHPVLTLSPEKALNFE
  GTKVTLHCETQEDSLRTLYRFYHEGVPLRHKSVRCERGASISFSLTTENSGNYYCTADNG
  LGAKPSKAVSLSVTVPVSHPVLNLSSPEDLIFEGAKVTLHCEAQRGSLPILYQFHHEGAA
  LERRSANSAGGVAISFSLTAEHSGNYYCTADNGFGPQRSKAVSLSVTVPVSHPVLTLSSA
  EALTFEGATVTLHCEVQRGSPQILYQFYHEDMPLWSSSTPSVGRVSFSFSLTEGHSGNYY
  CTADNGFGPQRSEVVSLFVTVPVSRPILTLRVPRAQAVVGDLLELHCEAPRGSPPILYWF
  YHEDVTLGSSSAPSGGEASFNLSLTAEHSGNYSCEANNGLVAQHSDTISLSVIVPVSRPI
  LTFRAPRAQAVVGDLLELHCEALRGSSPILYWFYHEDVTLGKISAPSGGGASFNLSLTTE
  HSGIYSCEADNGLEAQRSEMVTLKVAVPVSRPVLTLRAPGTHAAVGDLLELHCEALRGSP
  LILYRFFHEDVTLGNRSSPSGGASLNLSLTAEHSGNYSCEADNGLGAQRSETVTLYITGL
  TANRSGPFATGVAGGLLSIAGLAAGALLLYCWLSRKAGRKPASDPARSPSDSDSQEPTYH
  NVPAWEELQPVYTNANPRGENVVYSEVRIIQEKKKHAVASDPRHLRNKGSPIIYSEVKVA
  STPVSGSLFLASSAPHR
• Function: May be involved in B-cell development and differentiation in peripheral lymphoid organs and may be useful markers of B-cell stages. May have an immunoregulatory role in marginal zone B-cells. May play a role in fertilization.
• Tissue Specificity: Expressed in marginal zone B-cells, immunoblasts, tonsillar germinal center centrocytes and in the intraepithelial and interfollicular regions of the tonsil. Expressed in many lymphoma cell lines and on hairy cell leukemia cells. Isoform 1, isoform 3, isoform 4 and isoform 5 are detected in lymph node, spleen, bone marrow, and small intestine with preponderance of isoform 3. Expressed in mature and memory B-cells and down-regulated in germinal center cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[2]
Asthma	DISW9QNS	Strong	Genetic Variation	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[3]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[4]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[5]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[6]
B-cell neoplasm	DISVY326	Limited	Altered Expression	[5]
Burkitt lymphoma	DIS9D5XU	Limited	Altered Expression	[5]
Hairy cell leukaemia	DISTD2E5	Limited	Biomarker	[7]
Lymphoma	DISN6V4S	Limited	Altered Expression	[5]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Fc receptor-like protein 5 (FCRL5).	[8]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Fc receptor-like protein 5 (FCRL5).	[9]

1 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 Fc receptor-like protein 5 (FCRL5).	[10]

References

• [1] Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing.Cancer Cell. 2017 Mar 13;31(3):383-395. doi: 10.1016/j.ccell.2017.02.001. Epub 2017 Mar 2.
• [2] Genetic risk of FCRL3 and FCRL5 polymorphisms in children with asthma and allergic rhinitis in a Chinese Han population.Int J Pediatr Otorhinolaryngol. 2019 May;120:58-63. doi: 10.1016/j.ijporl.2019.02.015. Epub 2019 Feb 5.
• [3] Phase I study of the anti-FcRH5 antibody-drug conjugate DFRF4539A in relapsed or refractory multiple myeloma.Blood Cancer J. 2019 Feb 4;9(2):17. doi: 10.1038/s41408-019-0178-8.
• [4] Fc receptor-like 1-5 molecules are similarly expressed in progressive and indolent clinical subtypes of B-cell chronic lymphocytic leukemia.Int J Cancer. 2008 Nov 1;123(9):2113-9. doi: 10.1002/ijc.23751.
• [5] Immunoglobulin superfamily receptor translocation associated 2 protein on lymphoma cell lines and hairy cell leukemia cells detected by novel monoclonal antibodies.Clin Cancer Res. 2005 Jan 1;11(1):87-96.
• [6] A single-nucleotide polymorphism marker within the FCRL5 gene and HLA-B27 positive Han Chinese ankylosing spondylitis patients.Tissue Antigens. 2009 Oct;74(4):314-6. doi: 10.1111/j.1399-0039.2009.01335.x.
• [7] Sandwich ELISAs for soluble immunoglobulin superfamily receptor translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human sera.Clin Chem Lab Med. 2006;44(5):594-602. doi: 10.1515/CCLM.2006.115.
• [8] 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.
• [9] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [10] 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.