Molecule Information

General Information of the Molecule (ID: Mol04141)

• Name: OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) ,Homo sapiens
• Synonyms: Deubiquitinating enzyme OTUB2; OTU domain-containing ubiquitin aldehyde-binding protein 2; Otubain-2; Ubiquitin-specific-processing protease OTUB2
• Molecule Type: Protein
• Gene Name: OTUB2
• Gene ID: 78990
• Location: chr14:94026340-94048930[+]
• Sequence:
  MSETSFNLISEKCDILSILRDHPENRIYRRKIEELSKRFTAIRKTKGDGNCFYRALGYSY
  LESLLGKSREIFKFKERVLQTPNDLLAAGFEEHKFRNFFNAFYSVVELVEKDGSVSSLLK
  VFNDQSASDHIVQFLRLLTSAFIRNRADFFRHFIDEEMDIKDFCTHEVEPMATECDHIQI
  TALSQALSIALQVEYVDEMDTALNHHVFPEAATPSVYLLYKTSHYNILYAADKH
• 3D-structure: PDB ID: 4FJV; Classification: Hydrolase; Method: X-ray diffraction; Resolution: 2.05 Å
• Function: Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of 'Lys-11'-,'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains. .
• Uniprot ID: OTUB2_HUMAN
• Ensembl ID: ENSG00000089723
• HGNC ID: HGNC:20351

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Carboplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Ovarian cancer [ICD-11: 2C73.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Carboplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: HCC patients; Homo Sapiens
• Experiment for Molecule Alteration: Western blot analysis
• Mechanism Description: Functional experiments using both transgenic mouse models and human cancer-derived models confirmed the critical tumor-suppressive role of OTUB2 in ovarian cancer. Intriguingly, we identified sorting nexin 29 pseudogene 2 (SNX29P2), an ill-defined protein with biased expression in ovarian tissue, as a bona fide substrate of OTUB2. The deubiquitination and stabilization of SNX29P2 by OTUB2 promotes the interaction between the E3 ligase VHL and HIF-1alpha and results in HIF-1alpha degradation, consequently inhibiting the expression of CA9. Activation of CA9 restores OTUB2-mediated inhibition of glycolysis and tumor growth; thus, CA9 inhibitors might be a promising strategy for ovarian cancer treatment.

References

• Ref 1: OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition. Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2315348121.