Details of Drug Off-Target (DOT)

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

• DOT Name: Microtubule-associated tumor suppressor 1 (MTUS1)
• Synonyms: AT2 receptor-binding protein; Angiotensin-II type 2 receptor-interacting protein; Mitochondrial tumor suppressor 1
• Gene Name: MTUS1
• Related Disease:
  Bone osteosarcoma
  Osteosarcoma
  Acute erythroid leukemia
  Alzheimer disease
  Bladder cancer
  Breast neoplasm
  Carcinoma
  Colorectal carcinoma
  Diamond-Blackfan anemia
  Essential thrombocythemia
  Galactokinase deficiency
  Gastric cancer
  Hepatocellular carcinoma
  Immunodeficiency
  Lung cancer
  Lung carcinoma
  Marinesco-Sjogren syndrome
  Neoplasm
  Non-small-cell lung cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Advanced cancer
  Epithelial ovarian cancer
  Ovarian cancer
  Adenocarcinoma
  Invasive breast carcinoma
  Breast cancer
  Breast carcinoma
  Head-neck squamous cell carcinoma
  Hereditary breast carcinoma
  Leukoplakia
• UniProt ID: MTUS1_HUMAN
• Sequence:
  MTDDNSDDKIEDELQTFFTSDKDGNTHAYNPKSPPTQNSSASSVNWNSANPDDMVVDYET
  DPAVVTGENISLSLQGVEVFGHEKSSSDFISKQVLDMHKDSICQCPALVGTEKPKYLQHS
  CHSLEAVEGQSVEPSLPFVWKPNDNLNCAGYCDALELNQTFDMTVDKVNCTFISHHAIGK
  SQSFHTAGSLPPTGRRSGSTSSLSYSTWTSSHSDKTHARETTYDRESFENPQVTPSEAQD
  MTYTAFSDVVMQSEVFVSDIGNQCACSSGKVTSEYTDGSQQRLVGEKETQALTPVSDGME
  VPNDSALQEFFCLSHDESNSEPHSQSSYRHKEMGQNLRETVSYCLIDDECPLMVPAFDKS
  EAQVLNPEHKVTETEDTQMVSKGKDLGTQNHTSELILSSPPGQKVGSSFGLTWDANDMVI
  STDKTMCMSTPVLEPTKVTFSVSPIEATEKCKKVEKGNRGLKNIPDSKEAPVNLCKPSLG
  KSTIKTNTPIGCKVRKTEIISYPRPNFKNVKAKVMSRAVLQPKDAALSKVTPRPQQTSAS
  SPSSVNSRQQTVLSRTPRSDLNADKKAEILINKTHKQQFNKLITSQAVHVTTHSKNASHR
  VPRTTSAVKSNQEDVDKASSSNSACETGSVSALFQKIKGILPVKMESAECLEMTYVPNID
  RISPEKKGEKENGTSMEKQELKQEIMNETFEYGSLFLGSASKTTTTSGRNISKPDSCGLR
  QIAAPKAKVGPPVSCLRRNSDNRNPSADRAVSPQRIRRVSSSGKPTSLKTAQSSWVNLPR
  PLPKSKASLKSPALRRTGSTPSIASTHSELSTYSNNSGNAAVIKYEEKPPKPAFQNGSSG
  SFYLKPLVSRAHVHLMKTPPKGPSRKNLFTALNAVEKSRQKNPRSLCIQPQTAPDALPPE
  KTLELTQYKTKCENQSGFILQLKQLLACGNTKFEALTVVIQHLLSEREEALKQHKTLSQE
  LVNLRGELVTASTTCEKLEKARNELQTVYEAFVQQHQAEKTERENRLKEFYTREYEKLRD
  TYIEEAEKYKMQLQEQFDNLNAAHETSKLEIEASHSEKLELLKKAYEASLSEIKKGHEIE
  KKSLEDLLSEKQESLEKQINDLKSENDALNEKLKSEEQKRRAREKANLKNPQIMYLEQEL
  ESLKAVLEIKNEKLHQQDIKLMKMEKLVDNNTALVDKLKRFQQENEELKARMDKHMAISR
  QLSTEQAVLQESLEKESKVNKRLSMENEELLWKLHNGDLCSPKRSPTSSAIPLQSPRNSG
  SFPSPSISPR
• Function: Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth.
• Tissue Specificity: Ubiquitously expressed (at protein level). Highly expressed in brain. Down-regulated in ovarian carcinoma, pancreas carcinoma, colon carcinoma and head and neck squamous cell carcinoma (HNSCC). Isoform 1 is the major isoform in most peripheral tissues. Isoform 2 is abundant in most peripheral tissues. Isoform 3 is the major isoform in brain, female reproductive tissues, thyroid and heart. Within brain it is highly expressed in corpus callosum and pons. Isoform 6 is brain-specific, it is the major isoform in cerebellum and fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[6]
Diamond-Blackfan anemia	DISI2SNW	Strong	Biomarker	[7]
Essential thrombocythemia	DISWWK11	Strong	Genetic Variation	[8]
Galactokinase deficiency	DISEB0V4	Strong	Genetic Variation	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[11]
Immunodeficiency	DIS093I0	Strong	Biomarker	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[13]
Marinesco-Sjogren syndrome	DISKEU0B	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[16]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Prostate cancer	DISF190Y	Strong	Biomarker	[17]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[17]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[18]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[18]
Adenocarcinoma	DIS3IHTY	Disputed	Genetic Variation	[19]
Invasive breast carcinoma	DISANYTW	Disputed	Altered Expression	[20]
Breast cancer	DIS7DPX1	Limited	Biomarker	[15]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[15]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[21]
Hereditary breast carcinoma	DISAEZT5	Limited	Genetic Variation	[22]
Leukoplakia	DIST3QD3	Limited	Altered Expression	[23]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Microtubule-associated tumor suppressor 1 (MTUS1) decreases the response to substance of Arsenic trioxide.	[43]
Etoposide	DMNH3PG	Approved	Microtubule-associated tumor suppressor 1 (MTUS1) affects the response to substance of Etoposide.	[44]
Topotecan	DMP6G8T	Approved	Microtubule-associated tumor suppressor 1 (MTUS1) affects the response to substance of Topotecan.	[44]

17 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 Microtubule-associated tumor suppressor 1 (MTUS1).	[24]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[28]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[30]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[25]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[31]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[32]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[24]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[33]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[34]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[36]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[41]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Microtubule-associated tumor suppressor 1 (MTUS1).	[42]

4 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 Microtubule-associated tumor suppressor 1 (MTUS1).	[37]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Microtubule-associated tumor suppressor 1 (MTUS1).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Microtubule-associated tumor suppressor 1 (MTUS1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Microtubule-associated tumor suppressor 1 (MTUS1).	[40]

References

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