Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOT2OXM)

• DOT Name: STAM-binding protein (STAMBP)
• Synonyms: EC 3.4.19.-; Associated molecule with the SH3 domain of STAM; Endosome-associated ubiquitin isopeptidase
• Gene Name: STAMBP
• Related Disease:
  Brain disease
  Capillary malformation-arteriovenous malformation syndrome
  Microcephaly-capillary malformation syndrome
  Microlissencephaly
  Alopecia
  Alopecia areata
  Camptodactyly-arthropathy-coxa vara-pericarditis syndrome
  Epilepsy
  Isolated congenital microcephaly
  Head-neck squamous cell carcinoma
  Melanoma
• UniProt ID: STABP_HUMAN
• PDB ID: 2XZE; 3RZU; 3RZV; 5IXF
• EC Number: 3.4.19.-
• Pfam ID: PF01398 ; PF08969
• Sequence:
  MSDHGDVSLPPEDRVRALSQLGSAVEVNEDIPPRRYFRSGVEIIRMASIYSEEGNIEHAF
  ILYNKYITLFIEKLPKHRDYKSAVIPEKKDTVKKLKEIAFPKAEELKAELLKRYTKEYTE
  YNEEKKKEAEELARNMAIQQELEKEKQRVAQQKQQQLEQEQFHAFEEMIRNQELEKERLK
  IVQEFGKVDPGLGGPLVPDLEKPSLDVFPTLTVSSIQPSDCHTTVRPAKPPVVDRSLKPG
  ALSNSESIPTIDGLRHVVVPGRLCPQFLQLASANTARGVETCGILCGKLMRNEFTITHVL
  IPKQSAGSDYCNTENEEELFLIQDQQGLITLGWIHTHPTQTAFLSSVDLHTHCSYQMMLP
  ESVAIVCSPKFQETGFFKLTDHGLEEISSCRQKGFHPHSKDPPLFCSCSHVTVVDRAVTI
  TDLR
• Function: Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains. Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization. Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway: Metalloprotease DUBs (R-HSA-5689901)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brain disease	DIS6ZC3X	Definitive	Biomarker	[1]
Capillary malformation-arteriovenous malformation syndrome	DISMN03Q	Definitive	Biomarker	[1]
Microcephaly-capillary malformation syndrome	DISWBVBT	Definitive	Autosomal recessive	[1]
Microlissencephaly	DISUCKNT	Definitive	Biomarker	[1]
Alopecia	DIS37HU4	Strong	Genetic Variation	[2]
Alopecia areata	DIS0XXBJ	Strong	Genetic Variation	[2]
Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	DISZB072	Strong	Genetic Variation	[2]
Epilepsy	DISBB28L	Strong	Genetic Variation	[3]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[3]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[4]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of STAM-binding protein (STAMBP).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of STAM-binding protein (STAMBP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of STAM-binding protein (STAMBP).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of STAM-binding protein (STAMBP).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of STAM-binding protein (STAMBP).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of STAM-binding protein (STAMBP).	[11]
Aspirin	DM672AH	Approved	Aspirin increases the expression of STAM-binding protein (STAMBP).	[12]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 decreases the expression of STAM-binding protein (STAMBP).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of STAM-binding protein (STAMBP).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of STAM-binding protein (STAMBP).	[15]

References

• [1] Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. Nat Genet. 2013 May;45(5):556-62. doi: 10.1038/ng.2602. Epub 2013 Mar 31.
• [2] Novel STAMBP mutation and additional findings in an Arabic family.Am J Med Genet A. 2015 Apr;167A(4):805-9. doi: 10.1002/ajmg.a.36782. Epub 2015 Feb 18.
• [3] Earlyonset epilepsy and microcephalycapillary malformation syndrome caused by a novel STAMBP mutation in a Chinese boy.Mol Med Rep. 2019 Dec;20(6):5145-5151. doi: 10.3892/mmr.2019.10757. Epub 2019 Oct 17.
• [4] Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma.Cells. 2019 Nov 28;8(12):1535. doi: 10.3390/cells8121535.
• [5] STAM-binding protein regulates melanoma metastasis through SLUG stabilization.Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):484-488. doi: 10.1016/j.bbrc.2018.11.068. Epub 2018 Nov 16.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. Endocr Relat Cancer. 2007 Jun;14(2):305-15. doi: 10.1677/ERC-06-0003.
• [12] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [13] Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4. Oncol Rep. 2017 Nov;38(5):2705-2716. doi: 10.3892/or.2017.5989. Epub 2017 Sep 22.
• [14] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.