Details of Drug Off-Target (DOT)

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

• DOT Name: Nuclear body protein SP140 (SP140)
• Synonyms: Lymphoid-restricted homolog of Sp100; LYSp100; Nuclear autoantigen Sp-140; Speckled 140 kDa
• Gene Name: SP140
• Related Disease:
  Neoplasm
  Advanced cancer
  Autoimmune disease
  Cholangiocarcinoma
  Classic Hodgkin lymphoma
  Ehlers-Danlos syndrome
  Erectile dysfunction
  Hepatic veno-occlusive disease-immunodeficiency syndrome
  Nasopharyngeal carcinoma
  Obstructive sleep apnea
  Plasma cell myeloma
  Promyelocytic leukaemia
  Sarcoidosis
  Sclerosing cholangitis
  Ankylosing spondylitis
  Psoriasis
  Small lymphocytic lymphoma
  Ulcerative colitis
• UniProt ID: SP140_HUMAN
• PDB ID: 2MD7; 2MD8; 6G8R
• Pfam ID: PF00439 ; PF03172 ; PF00628 ; PF01342
• Sequence:
  MAQQGQQGQMASGDSNLNFRMVAEIQNVEGQNLQEQVCPEPIFRFFRENKVEIASAITRP
  FPFLMGLRDRSFISEQMYEHFQEAFRNLVPVTRVMYCVLSELEKTFGWSHLEALFSRINL
  MAYPDLNEIYRSFQNVCYEHSPLQMNNVNDLEDRPRLLPYGKQENSNACHEMDDIAVPQE
  ALSSSPRCEPGFSSESCEQLALPKAGGGDAEDAPSLLPGGGVSCKLAIQIDEGESEEMPK
  LLPYDTEVLESNGMIDAARTYSTAPGEKQGEEEGRNSPRKRNQDKEKYQESPEGRDKETF
  DLKTPQVTNEGEPEKGLCLLPGEGEEGSDDCSEMCDGEEPQEASSSLARCGSVSCLSAET
  FDLKTPQVTNEGEPEKELSLLPGEGEEGSDDCSEMCDGEERQEASSSLARRGSVSSELEN
  HPMNEEGESEELASSLLYDNVPGAEQSAYENEKCSCVMCFSEEVPGSPEARTESDQACGT
  MDTVDIANNSTLGKPKRKRRKKRGHGWSRMRMRRQENSQQNDNSKADGQVVSSEKKANVN
  LKDLSKIRGRKRGKPGTRFTQSDRAAQKRVRSRASRKHKDETVDFKAPLLPVTCGGVKGI
  LHKKKLQQGILVKCIQTEDGKWFTPTEFEIKGGHARSKNWRLSVRCGGWPLRWLMENGFL
  PDPPRIRYRKKKRILKSQNNSSVDPCMRNLDECEVCRDGGELFCCDTCSRVFHEDCHIPP
  VEAERTPWNCIFCRMKESPGSQQCCQESEVLERQMCPEEQLKCEFLLLKVYCCSESSFFA
  KIPYYYYIREACQGLKEPMWLDKIKKRLNEHGYPQVEGFVQDMRLIFQNHRASYKYKDFG
  QMGFRLEAEFEKNFKEVFAIQETNGNN
• Function: Component of the nuclear body, also known as nuclear domain 10, PML oncogenic domain, and KR body. May be involved in the pathogenesis of acute promyelocytic leukemia and viral infection. May play a role in chromatin-mediated regulation of gene expression although it does not bind to histone H3 tails.
• Tissue Specificity: High levels in spleen and peripheral blood leukocytes, much lower levels in tonsils, thymus, prostate, ovary, small intestine, and colon . Very low levels in heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas . Not detected in brain, liver and muscle .

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[3]
Cholangiocarcinoma	DIS71F6X	Strong	Genetic Variation	[4]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[5]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Biomarker	[6]
Erectile dysfunction	DISD8MTH	Strong	Genetic Variation	[7]
Hepatic veno-occlusive disease-immunodeficiency syndrome	DIS000H0	Strong	Genetic Variation	[8]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[9]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[6]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[5]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[10]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[11]
Sclerosing cholangitis	DIS7GZNB	Strong	Genetic Variation	[4]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[12]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[12]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[13]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Nuclear body protein SP140 (SP140) affects the response to substance of Paclitaxel.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nuclear body protein SP140 (SP140).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nuclear body protein SP140 (SP140).	[16]

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 increases the methylation of Nuclear body protein SP140 (SP140).	[15]

References

• [1] Post-GWAS functional characterization of susceptibility variants for chronic lymphocytic leukemia.PLoS One. 2012;7(1):e29632. doi: 10.1371/journal.pone.0029632. Epub 2012 Jan 3.
• [2] Sp140 is a multi-SUMO-1 target and its PHD finger promotes SUMOylation of the adjacent Bromodomain.Biochim Biophys Acta Gen Subj. 2019 Feb;1863(2):456-465. doi: 10.1016/j.bbagen.2018.11.011. Epub 2018 Nov 19.
• [3] SP140 regulates the expression of immune-related genes associated with multiple sclerosis and other autoimmune diseases by NF-B inhibition.Hum Mol Genet. 2018 Dec 1;27(23):4012-4023. doi: 10.1093/hmg/ddy284.
• [4] Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.Gut. 2018 Aug;67(8):1517-1524. doi: 10.1136/gutjnl-2016-313598. Epub 2017 Aug 4.
• [5] Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci.Sci Rep. 2017 Jan 23;7:41071. doi: 10.1038/srep41071.
• [6] Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.Sleep. 2016 Apr 1;39(4):743-55. doi: 10.5665/sleep.5620.
• [7] Pilot genome-wide association search identifies potential loci for risk of erectile dysfunction in type 1 diabetes using the DCCT/EDIC study cohort.J Urol. 2012 Aug;188(2):514-20. doi: 10.1016/j.juro.2012.04.001. Epub 2012 Jun 15.
• [8] Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome.J Allergy Clin Immunol. 2012 Sep;130(3):735-742.e6. doi: 10.1016/j.jaci.2012.02.054. Epub 2012 May 21.
• [9] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
• [10] Identification and characterization of a leukocyte-specific component of the nuclear body.J Biol Chem. 1996 Nov 15;271(46):29198-204. doi: 10.1074/jbc.271.46.29198.
• [11] Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk.Am J Respir Crit Care Med. 2015 Sep 15;192(6):727-36. doi: 10.1164/rccm.201503-0418OC.
• [12] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [13] Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.Nat Commun. 2017 Feb 6;8:14175. doi: 10.1038/ncomms14175.
• [14] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [15] 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.
• [16] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [17] 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.