Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGY26U4)

• DOT Name: SPRY domain-containing SOCS box protein 1 (SPSB1)
• Synonyms: SSB-1
• Gene Name: SPSB1
• Related Disease:
  Ataxia-telangiectasia
  Breast cancer
  Breast carcinoma
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Pancytopenia
  Rheumatoid arthritis
  Schnyder corneal dystrophy
  Acute myelogenous leukaemia
  Advanced cancer
  Obesity
  Respiratory failure
  Asthma
  Neoplasm
• UniProt ID: SPSB1_HUMAN
• PDB ID: 2JK9; 3F2O
• Pfam ID: PF07525 ; PF00622
• Sequence:
  MGQKVTGGIKTVDMRDPTYRPLKQELQGLDYCKPTRLDLLLDMPPVSYDVQLLHSWNNND
  RSLNVFVKEDDKLIFHRHPVAQSTDAIRGKVGYTRGLHVWQITWAMRQRGTHAVVGVATA
  DAPLHSVGYTTLVGNNHESWGWDLGRNRLYHDGKNQPSKTYPAFLEPDETFIVPDSFLVA
  LDMDDGTLSFIVDGQYMGVAFRGLKGKKLYPVVSAVWGHCEIRMRYLNGLDPEPLPLMDL
  CRRSVRLALGRERLGEIHTLPLPASLKAYLLYQ
• Function: Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2. Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Pancytopenia	DISVKEHV	Strong	Biomarker	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[5]
Schnyder corneal dystrophy	DISAYSN1	Strong	Biomarker	[6]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[7]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[8]
Obesity	DIS47Y1K	moderate	Genetic Variation	[9]
Respiratory failure	DISVMYJO	moderate	Biomarker	[8]
Asthma	DISW9QNS	Limited	Genetic Variation	[10]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[8]

20 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 SPRY domain-containing SOCS box protein 1 (SPSB1).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[17]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[20]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[21]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[22]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[23]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[24]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[25]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[29]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[30]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of SPRY domain-containing SOCS box protein 1 (SPSB1).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of SPRY domain-containing SOCS box protein 1 (SPSB1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of SPRY domain-containing SOCS box protein 1 (SPSB1).	[28]

References

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• [4] Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress.Blood. 2017 May 4;129(18):2479-2492. doi: 10.1182/blood-2016-06-725093. Epub 2017 Mar 7.
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• [13] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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• [20] 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.
• [21] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [22] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
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• [24] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [25] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [26] Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
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• [28] 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.
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