Details for: OTUB2

Gene ID: 78990

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: OTUB2

Ensembl ID: ENSG00000089723

Description: OTU deubiquitinase, ubiquitin aldehyde binding 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • placental villous trophoblast CL2000060
    CSI 5.03
    rCSI 7.77%
    PRS 99.8

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [OTUB2](/details-gene/78990) (OTU Deubiquitinase, Ubiquitin Aldehyde Binding 2) is a protein-coding gene that encodes a deubiquitinating enzyme (DUB) belonging to the ovarian tumor (OTU) superfamily of cysteine proteases ([Link](https://doi.org/10.1038/sj.embor.embor824)). The primary function of the [OTUB2](/details-gene/78990) protein is to remove ubiquitin moieties from substrate proteins, thereby regulating their stability, activity, and localization. Functional annotations indicate its involvement in processing diverse ubiquitin chain linkages, suggesting a role in multiple cellular processes from protein degradation to signal transduction. **Overall**, expression data highlight [OTUB2](/details-gene/78990) as a particularly significant gene in the [placental villous trophoblast](/details-cell/CL2000060), implying a specialized function in placental development and maternal-fetal homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [OTUB2](/details-gene/78990) suggests a highly specialized role, with the most significant expression observed in the [placental villous trophoblast](/details-cell/CL2000060) (CSI: 5.03). These cells are fundamental components of the placenta, forming the primary interface between maternal and fetal tissues. They are critical for nutrient exchange, hormone production, and establishing immune tolerance during pregnancy. The prominent role of [OTUB2](/details-gene/78990) in this cell type suggests it is a key regulator of protein turnover and signaling pathways essential for trophoblast function. By modulating the ubiquitination status of target proteins, [OTUB2](/details-gene/78990) may influence processes such as cell differentiation, proliferation, and invasion, which are all tightly controlled during placentation. The nuclear localization of the protein further suggests it could regulate the stability of transcription factors or other nuclear proteins that direct trophoblast development programs. The absence of significant expression scores in other cell types within the provided data underscores its potential as a specific molecular player in the unique biology of the placenta. ## Pathways and Molecular Function [OTUB2](/details-gene/78990) is an active cysteine protease whose molecular function is defined by its [cysteine-type deubiquitinase activity](/term/GO:0004843). It is a key component of the [Deubiquitination](/content/detail/R-HSA-5688426) machinery, which is part of the broader cellular process of [Post-translational protein modification](/content/detail/R-HSA-597592). The enzyme participates directly in the biological process of [protein deubiquitination](/term/GO:0016579). Research has demonstrated its capacity to cleave various ubiquitin chain linkages, including K11, K48, and K63 ([Link](https://doi.org/10.1016/j.cell.2013.05.046)). This versatility implies that [OTUB2](/details-gene/78990) can influence a wide range of cellular outcomes: * **K48-linked deubiquitination** ([GO:0071108](https://www.ebi.ac.uk/QuickGO/term/GO:0071108)) typically rescues proteins from proteasomal degradation, thereby controlling their abundance. * **K63-linked deubiquitination** ([GO:0070536](https://www.ebi.ac.uk/QuickGO/term/GO:0070536)) often modulates protein activity and signaling cascades, such as those involved in immune responses and DNA damage repair. Consistent with its role in regulating protein fate, [OTUB2](/details-gene/78990) is annotated to the [Metabolism of proteins](/content/detail/R-HSA-392499) pathway. Its localization to the [nucleus](/term/GO:0005634) suggests that its substrates are likely nuclear proteins, potentially impacting gene expression and cell cycle control within the [placental villous trophoblast](/details-cell/CL2000060). ## Research Directions The specific and significant expression of [OTUB2](/details-gene/78990) in [placental villous trophoblast](/details-cell/CL2000060) points toward a critical, yet under-investigated, role in pregnancy and placental pathology. Its function as a deubiquitinase makes it a plausible regulator of the delicate cellular processes required for a successful pregnancy. **Proposed Hypotheses:** 1. **[OTUB2](/details-gene/78990) is a critical regulator of trophoblast invasion and differentiation.** By deubiquitinating and stabilizing key transcription factors or cell cycle regulators, [OTUB2](/details-gene/78990) may control the transition of trophoblasts into their invasive phenotype. Dysregulation of [OTUB2](/details-gene/78990) activity could therefore contribute to pregnancy disorders characterized by abnormal placentation, such as pre-eclampsia or intrauterine growth restriction. 2. **[OTUB2](/details-gene/78990) modulates the immune environment at the maternal-fetal interface.** The ubiquitination pathway is central to immune signaling. [OTUB2](/details-gene/78990) could deubiquitinate key signaling molecules in trophoblasts, altering their cytokine and chemokine secretion profile to maintain a state of immune tolerance and prevent maternal immune rejection of the semi-allogeneic fetus. **Experimental Approach:** To test the hypothesis that [OTUB2](/details-gene/78990) regulates trophoblast invasion, one could utilize an *in vitro* model. CRISPR-Cas9-mediated knockout of [OTUB2](/details-gene/78990) could be performed in a human trophoblast cell line (e.g., HTR-8/SVneo). The functional consequences would be assessed using a Matrigel transwell invasion assay to quantify invasive capacity. Furthermore, changes in the expression of key differentiation markers (e.g., human chorionic gonadotropin, syncytin) could be measured by qPCR and ELISA. To identify direct substrates, immunoprecipitation of [OTUB2](/details-gene/78990) followed by mass spectrometry (IP-MS) could be performed to discover its binding partners, and proteomic analysis of the knockout cells could reveal proteins with increased ubiquitination levels. **Therapeutic Potential:** As an enzyme, [OTUB2](/details-gene/78990) is a potentially druggable target for small molecule inhibitors or activators. Its highly specific expression in trophoblasts suggests that modulating its activity could have targeted effects on placental function with minimal systemic side effects for the mother. If aberrant [OTUB2](/details-gene/78990) activity is implicated in pregnancy disorders, it could become a novel therapeutic target. For instance, in conditions of insufficient placental invasion like pre-eclampsia, a small molecule activator of [OTUB2](/details-gene/78990) might promote necessary trophoblast functions. Conversely, in pathologies involving excessive trophoblast proliferation or invasion, such as choriocarcinoma, an [OTUB2](/details-gene/78990) inhibitor could represent a targeted therapeutic strategy.

Genular Protein ID: 1547512582

Symbol: OTUB2_HUMAN

Name: Ubiquitin thioesterase OTUB2

UniProtKB Accession Codes:

Q96DC9 Q6IA10 Q9H6T1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTC 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 6 Ensembl 4 EvolutionaryTrace 1 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 15 PDBsum 15 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12704427

Title: Otubains: a new family of cysteine proteases in the ubiquitin pathway.

PubMed ID: 12704427

DOI: 10.1038/sj.embor.embor824

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18954305

Title: Structural basis and specificity of human otubain 1-mediated deubiquitination.

PubMed ID: 18954305

DOI: 10.1042/bj20081318

PubMed ID: 23827681

Title: OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis.

PubMed ID: 23827681

DOI: 10.1016/j.cell.2013.05.046

PubMed ID: 15258613

Title: Crystal structure of human otubain 2.

PubMed ID: 15258613

DOI: 10.1038/sj.embor.7400201

Sequence Information:

  • Length: 234
  • Mass: 27213
  • Checksum: DF2DBD32A78F9929
  • Sequence:
    • MSETSFNLIS EKCDILSILR DHPENRIYRR KIEELSKRFT AIRKTKGDGN CFYRALGYSY 
LESLLGKSRE IFKFKERVLQ TPNDLLAAGF EEHKFRNFFN AFYSVVELVE KDGSVSSLLK 
VFNDQSASDH IVQFLRLLTS AFIRNRADFF RHFIDEEMDI KDFCTHEVEP MATECDHIQI 
TALSQALSIA LQVEYVDEMD TALNHHVFPE AATPSVYLLY KTSHYNILYA ADKH