Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7MDF09)

• DOT Name: Signaling threshold-regulating transmembrane adapter 1 (SIT1)
• Synonyms: SHP2-interacting transmembrane adapter protein; Suppression-inducing transmembrane adapter 1; gp30/40
• Gene Name: SIT1
• Related Disease:
  Advanced cancer
  Allergic asthma
  Allergic rhinitis
  Alzheimer disease
  Dementia
  Drug-resistant tuberculosis
  Prostate cancer
  Prostate carcinoma
  Rhinitis
  Tuberculosis
  Cholestasis
  Non-insulin dependent diabetes
  Multi-drug resistant tuberculosis
  Obesity
• UniProt ID: SIT1_HUMAN
• Sequence:
  MNQADPRLRAVCLWTLTSAAMSRGDNCTDLLALGIPSITQAWGLWVLLGAVTLLFLISLA
  AHLSQWTRGRSRSHPGQGRSGESVEEVPLYGNLHYLQTGRLSQDPEPDQQDPTLGGPARA
  AEEVMCYTSLQLRPPQGRIPGPGTPVKYSEVVLDSEPKSQASGPEPELYASVCAQTRRAR
  ASFPDQAYANSQPAAS
• Function: Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells. Involved in positive selection of T-cells.
• Tissue Specificity: Specifically expressed in T- and B-cells. Present in plasma cells but not in germinal center B-cells (at protein level). Expressed in T- and B-cell lymphoma.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Biomarker	[2]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Dementia	DISXL1WY	Strong	Biomarker	[4]
Drug-resistant tuberculosis	DIS5BUFB	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[6]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[6]
Rhinitis	DISKLMN7	Strong	Biomarker	[7]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[8]
Cholestasis	DISDJJWE	moderate	Biomarker	[9]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Genetic Variation	[10]
Multi-drug resistant tuberculosis	DIS1A2CS	Limited	Genetic Variation	[11]
Obesity	DIS47Y1K	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Signaling threshold-regulating transmembrane adapter 1 (SIT1) increases the Neutropenia ADR of Chlorothiazide.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Signaling threshold-regulating transmembrane adapter 1 (SIT1).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Signaling threshold-regulating transmembrane adapter 1 (SIT1).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Signaling threshold-regulating transmembrane adapter 1 (SIT1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Signaling threshold-regulating transmembrane adapter 1 (SIT1).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Signaling threshold-regulating transmembrane adapter 1 (SIT1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Signaling threshold-regulating transmembrane adapter 1 (SIT1).	[18]

References

• [1] Exploring Associations of Sedentary Behavior and Physical Activity with Quality of Life in Young Adult Cancer Survivors.J Adolesc Young Adult Oncol. 2018 Dec;7(6):643-651. doi: 10.1089/jayao.2018.0032. Epub 2018 Jul 23.
• [2] Dust mite allergen-specific immunotherapy increases IL4 DNA methylation and induces Der p-specific T cell tolerance in children with allergic asthma.Cell Mol Immunol. 2018 Nov;15(11):963-972. doi: 10.1038/cmi.2017.26. Epub 2017 Jun 26.
• [3] In vivo and in vitro studies of Th17 response to specific immunotherapy in house dust mite-induced allergic rhinitis patients.PLoS One. 2014 Mar 19;9(3):e91950. doi: 10.1371/journal.pone.0091950. eCollection 2014.
• [4] Intact global cognitive and olfactory ability predicts lack of transition to dementia.Alzheimers Dement. 2020 Feb;16(2):326-334. doi: 10.1016/j.jalz.2019.08.200. Epub 2020 Jan 4.
• [5] Genotypic diversity of multidrug-, quinolone- and extensively drug-resistant Mycobacterium tuberculosis isolates in Thailand.Infect Genet Evol. 2015 Jun;32:432-9. doi: 10.1016/j.meegid.2015.03.038. Epub 2015 Apr 4.
• [6] New sparse implantation technique of I-125 low-dose-rate brachytherapy using concomitant short-term hormonal treatment for low and intermediate-risk prostate cancer: An initial study of therapeutic feasibility.Sci Rep. 2019 Dec 10;9(1):18674. doi: 10.1038/s41598-019-55317-1.
• [7] Specific immunotherapy in allergic rhinitis.Eur Ann Otorhinolaryngol Head Neck Dis. 2017 Sep;134(4):253-258. doi: 10.1016/j.anorl.2017.06.005. Epub 2017 Jul 3.
• [8] Genetic Structure and Drug Susceptibility Patterns of Mycobacterium tuberculosis Complex Strains Responsible of Human Pulmonary Tuberculosis in the Major Rearing Region in Cameroon.Biomed Res Int. 2016;2016:2904832. doi: 10.1155/2016/2904832. Epub 2016 Dec 29.
• [9] From the Cover: MechanisticInsights in Cytotoxic and Cholestatic Potential of the Endothelial Receptor Antagonists Using HepaRG Cells. Toxicol Sci. 2017 Jun 1;157(2):451-464. doi: 10.1093/toxsci/kfx062.
• [10] Interrupting prolonged sitting in type 2 diabetes: nocturnal persistence of improved glycaemic control.Diabetologia. 2017 Mar;60(3):499-507. doi: 10.1007/s00125-016-4169-z. Epub 2016 Dec 9.
• [11] Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection.Am J Trop Med Hyg. 2016 Dec 7;95(6):1239-1246. doi: 10.4269/ajtmh.15-0711. Epub 2016 Oct 24.
• [12] Morning exercise mitigates the impact of prolonged sitting on cerebral blood flow in older adults.J Appl Physiol (1985). 2019 Apr 1;126(4):1049-1055. doi: 10.1152/japplphysiol.00001.2019. Epub 2019 Feb 7.
• [13] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [17] 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.
• [18] 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.
• [19] Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.