Details for: USP2

Gene ID: 9099

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: USP2

Ensembl ID: ENSG00000036672

Description: ubiquitin specific peptidase 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • vascular associated smooth muscle cell CL0000359
    CSI 4.95
    rCSI 16.06%
    PRS 92.97
  • myofibroblast cell CL0000186
    CSI 4.87
    rCSI 6.74%
    PRS 91.88
  • Mueller cell CL0000636
    CSI 4.86
    rCSI 11.09%
    PRS 89.5
  • retinal rod cell CL0000604
    CSI 4.34
    rCSI 7.65%
    PRS 90.86
  • ON-bipolar cell CL0000749
    CSI 3.19
    rCSI 4.74%
    PRS 92.79
  • perivascular cell CL4033054
    CSI 3.14
    rCSI 4.29%
    PRS 96.43
  • pancreatic D cell CL0000173
    CSI 2.95
    rCSI 2.9%
    PRS 95.11
  • pancreatic A cell CL0000171
    CSI 2.82
    rCSI 2.96%
    PRS 95.3
  • epithelial cell of proximal tubule CL0002306
    CSI 2.71
    rCSI 6.62%
    PRS 89.32
  • ciliated cell CL0000064
    CSI 2.69
    rCSI 4.35%
    PRS 89.03
  • ciliated epithelial cell CL0000067
    CSI 2.65
    rCSI 2.33%
    PRS 87.42
  • early lymphoid progenitor CL0000936
    CSI 2.63
    rCSI 2.31%
    PRS 96.39
  • OFF-bipolar cell CL0000750
    CSI 2.49
    rCSI 3.41%
    PRS 92.25
  • retinal cone cell CL0000573
    CSI 2.47
    rCSI 3.97%
    PRS 88
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.39
    rCSI 5.35%
    PRS 85.36
  • colon epithelial cell CL0011108
    CSI 2.34
    rCSI 2.45%
    PRS 92.3
  • rod bipolar cell CL0000751
    CSI 2.26
    rCSI 4.06%
    PRS 90.49
  • multi-ciliated epithelial cell CL0005012
    CSI 2.25
    rCSI 2.25%
    PRS 89.68
  • enterocyte CL0000584
    CSI 2.22
    rCSI 3.58%
    PRS 91.42
  • retinal bipolar neuron CL0000748
    CSI 2.11
    rCSI 3.95%
    PRS 88.21
  • type B pancreatic cell CL0000169
    CSI 2.1
    rCSI 4.66%
    PRS 94.14
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.08
    rCSI 2.48%
    PRS 85.1
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.07
    rCSI 2.58%
    PRS 83.01
  • microcirculation associated smooth muscle cell CL0008035
    CSI 2.03
    rCSI 5.88%
    PRS 93.67
  • lung ciliated cell CL1000271
    CSI 2.02
    rCSI 2.34%
    PRS 90.08
  • choroid plexus epithelial cell CL0000706
    CSI 2.01
    rCSI 3.28%
    PRS 89.23
  • colonocyte CL1000347
    CSI 1.98
    rCSI 2.84%
    PRS 92.48
  • cardiac muscle cell CL0000746
    CSI 1.94
    rCSI 2.79%
    PRS 87.93
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.86
    rCSI 4.82%
    PRS 92.58
  • muscle cell CL0000187
    CSI 1.73
    rCSI 3.54%
    PRS 95.41
  • regular atrial cardiac myocyte CL0002129
    CSI 1.66
    rCSI 5.34%
    PRS 91.14
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.65
    rCSI 2.78%
    PRS 85.23
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.65
    rCSI 5.17%
    PRS 87.73
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.63
    rCSI 3.72%
    PRS 88.32
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.53
    rCSI 2.46%
    PRS 85.96
  • basal cell of epidermis CL0002187
    CSI 1.25
    rCSI 2.22%
    PRS 69.54
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.12
    rCSI 2.71%
    PRS 83.17
  • glial cell CL0000125
    CSI 0.92
    rCSI 3.5%
    PRS 89.15
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.88
    rCSI 5.17%
    PRS 85.49
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.83
    rCSI 2.59%
    PRS 86.11
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.72
    rCSI 2.73%
    PRS 85.27
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.66
    rCSI 2.36%
    PRS 83.46
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.58
    rCSI 3.6%
    PRS 89.29
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.31
    rCSI 7.51%
    PRS 82.79
  • direct pathway medium spiny neuron CL4023026
    CSI 0.3
    rCSI 7.16%
    PRS 82.94

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

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 [USP2](/details-gene/9099) (Ubiquitin Specific Peptidase 2) is a protein-coding gene that encodes a deubiquitinating enzyme (DUB) belonging to the cysteine-type peptidase family. The primary function of [USP2](/details-gene/9099) is to remove ubiquitin from target proteins, thereby regulating their stability, localization, and activity. This enzymatic activity implicates [USP2](/details-gene/9099) in numerous fundamental cellular processes, including protein stabilization, cell cycle progression, circadian rhythm, and the regulation of key signaling pathways such as TP53 and TNF. **Overall**, expression data reveals its highest significance in structural and contractile cells, such as [vascular associated smooth muscle cell](/details-cell/CL0000359) and [myofibroblast cell](/details-cell/CL0000186), as well as a striking enrichment across various cell types of the retina, suggesting specialized roles in both tissue maintenance and neurobiology. ## Cellular Roles and Expression Landscape The expression profile of [USP2](/details-gene/9099) indicates its importance across a diverse range of specialized tissues. The **Overall** context highlights its most significant expression in cells associated with structural integrity and contractility, including [vascular associated smooth muscle cell](/details-cell/CL0000359), [myofibroblast cell](/details-cell/CL0000186), and [perivascular cell](/details-cell/CL4033054). This suggests a critical role for [USP2](/details-gene/9099)-mediated protein turnover in the function of these mechanically active cell types. A second major site of high significance is the retina. [USP2](/details-gene/9099) shows prominent expression in [Mueller cell](/details-cell/CL0000636), which are the principal glial cells of the retina, as well as in photoreceptor cells ([retinal rod cell](/details-cell/CL0000604) and [retinal cone cell](/details-cell/CL0000573)) and interneurons ([ON-bipolar cell](/details-cell/CL0000749) and [OFF-bipolar cell](/details-cell/CL0000750)). This distinct pattern points towards a specialized function in retinal physiology, potentially related to the high protein turnover required for phototransduction or the regulation of the circadian clock, a process in which [USP2](/details-gene/9099) is functionally implicated. Beyond these primary sites, [USP2](/details-gene/9099) is also significantly expressed in several other specialized cells, including endocrine cells of the pancreas ([pancreatic D cell](/details-cell/CL0000173) and [pancreatic A cell](/details-cell/CL0000171)), [epithelial cell of proximal tubule](/details-cell/CL0002306) in the kidney, and [astrocyte of the cerebral cortex](/details-cell/CL0002605), indicating its broad involvement in maintaining cellular homeostasis across multiple organ systems. ## Pathways and Molecular Function Functionally, [USP2](/details-gene/9099) is characterized by its [cysteine-type deubiquitinase activity](https://www.ebi.ac.uk/QuickGO/term/GO:0004843), enabling it to cleave ubiquitin from substrate proteins. This core function is central to its role in the [protein deubiquitination](https://www.ebi.ac.uk/QuickGO/term/GO:0016579) and [protein stabilization](https://www.ebi.ac.uk/QuickGO/term/GO:0050821) biological processes. [USP2](/details-gene/9099) is a well-documented regulator of the TP53 tumor suppressor pathway. It achieves this by targeting and deubiquitinating Mdm2, the primary E3 ubiquitin ligase for TP53, thereby stabilizing Mdm2 and promoting TP53 degradation [Link](https://doi.org/10.1038/sj.emboj.7601567). Similarly, it has been shown to deubiquitinate and stabilize MdmX, another key negative regulator of TP53 [Link](https://doi.org/10.1038/onc.2009.330). These activities are reflected in its annotation to pathways such as [Regulation of tp53 degradation](https://reactome.org/content/detail/R-HSA-6804757). The enzyme also plays a significant role in cell cycle control, as indicated by its involvement in the [positive regulation of mitotic cell cycle](https://www.ebi.ac.uk/QuickGO/term/GO:0045931) and its ability to bind cyclins. Specifically, [USP2](/details-gene/9099) has been reported to deubiquitinate and stabilize Cyclin D1, a critical regulator of the G1/S phase transition, thereby promoting cell proliferation [Link](https://doi.org/10.1016/j.molcel.2009.10.018). Additionally, functional annotations link [USP2](/details-gene/9099) to the regulation of [Tnf signaling](https://reactome.org/content/detail/R-HSA-75893) and [circadian regulation of gene expression](https://www.ebi.ac.uk/QuickGO/term/GO:0032922), highlighting its multifaceted role in modulating inflammatory responses and maintaining daily biological rhythms. ## Research Directions The diverse expression pattern and critical regulatory functions of [USP2](/details-gene/9099) suggest several avenues for future investigation. Its role as a stabilizer of proteins involved in cell growth and survival makes it a compelling subject in the context of proliferative diseases. Based on the available data, several testable hypotheses can be proposed: 1. Given its high expression in photoreceptors and its known role in circadian regulation, [USP2](/details-gene/9099) is essential for maintaining protein homeostasis within the phototransduction cascade and for entraining the retinal circadian clock. Its loss-of-function may lead to photoreceptor degeneration. 2. In [vascular associated smooth muscle cell](/details-cell/CL0000359), [USP2](/details-gene/9099) acts as a pro-proliferative factor by stabilizing Cyclin D1, and its overexpression contributes to the pathogenesis of vascular proliferative disorders such as atherosclerosis or restenosis. 3. [USP2](/details-gene/9099) modulates inflammatory signaling in retinal [Mueller cell](/details-cell/CL0000636) by regulating the ubiquitination status of key components within the [Tnf signaling](https://reactome.org/content/detail/R-HSA-75893) pathway, thereby influencing glial activation and neuroinflammation in the retina. A key experiment to test the second hypothesis would be to use a conditional knockout mouse model where [USP2](/details-gene/9099) is specifically deleted in smooth muscle cells. These mice could then be subjected to a vascular injury model (e.g., carotid artery ligation). The extent of neointimal hyperplasia could be quantified and compared between knockout and wild-type animals. In parallel, primary smooth muscle cells isolated from these mice could be analyzed for proliferation rates and levels of Cyclin D1 and other cell cycle regulators. **Therapeutic Potential** [USP2](/details-gene/9099) represents a promising therapeutic target, particularly for oncology. Because it stabilizes oncoproteins such as Mdm2 and Cyclin D1, **inhibition** of its deubiquitinase activity is a viable strategy to destabilize these proteins and suppress tumor growth. Small molecule inhibitors targeting [USP2](/details-gene/9099) could be developed as anti-cancer agents. Furthermore, its high expression in [myofibroblast cell](/details-cell/CL0000186) suggests it may also be a target for anti-fibrotic therapies. A potential challenge for systemic therapy is its broad expression in healthy tissues like the retina and kidney; therefore, targeted drug delivery or the development of highly specific inhibitors would be critical to minimize off-target effects.

Genular Protein ID: 3096477453

Symbol: UBP2_HUMAN

Name: Ubiquitin carboxyl-terminal hydrolase 2

UniProtKB Accession Codes:

O75604 B0YJB8 E9PPM2 Q8IUM2 Q8IW04 Q96MB9 Q9BQ21

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CORUM 1 CTD 1 ChEBI 4 ChEMBL 1 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 EC 2 EMBL 13 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 22 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 MoonDB 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 8 PDBsum 8 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 Reactome 5 RefSeq 5 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

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: 17290220

Title: The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2.

PubMed ID: 17290220

DOI: 10.1038/sj.emboj.7601567

PubMed ID: 19917254

Title: Suppression of cancer cell growth by promoting cyclin D1 degradation.

PubMed ID: 19917254

DOI: 10.1016/j.molcel.2009.10.018

PubMed ID: 19838211

Title: MdmX is a substrate for the deubiquitinating enzyme USP2a.

PubMed ID: 19838211

DOI: 10.1038/onc.2009.330

PubMed ID: 20403044

Title: Expression of USP2-69 in mesangial cells in vivo and in vitro.

PubMed ID: 20403044

DOI: 10.1111/j.1440-1827.2010.02496.x

PubMed ID: 22024150

Title: Deubiquitylating enzyme USP2 counteracts Nedd4-2-mediated downregulation of KCNQ1 potassium channels.

PubMed ID: 22024150

DOI: 10.1016/j.hrthm.2011.10.026

PubMed ID: 16905103

Title: Structural basis of ubiquitin recognition by the deubiquitinating protease USP2.

PubMed ID: 16905103

DOI: 10.1016/j.str.2006.06.012

Sequence Information:

  • Length: 605
  • Mass: 68072
  • Checksum: AFF4DA9344D21812
  • Sequence:
    • MSQLSSTLKR YTESARYTDA HYAKSGYGAY TPSSYGANLA ASLLEKEKLG FKPVPTSSFL 
TRPRTYGPSS LLDYDRGRPL LRPDITGGGK RAESQTRGTE RPLGSGLSGG SGFPYGVTNN 
CLSYLPINAY DQGVTLTQKL DSQSDLARDF SSLRTSDSYR IDPRNLGRSP MLARTRKELC 
TLQGLYQTAS CPEYLVDYLE NYGRKGSASQ VPSQAPPSRV PEIISPTYRP IGRYTLWETG 
KGQAPGPSRS SSPGRDGMNS KSAQGLAGLR NLGNTCFMNS ILQCLSNTRE LRDYCLQRLY 
MRDLHHGSNA HTALVEEFAK LIQTIWTSSP NDVVSPSEFK TQIQRYAPRF VGYNQQDAQE 
FLRFLLDGLH NEVNRVTLRP KSNPENLDHL PDDEKGRQMW RKYLEREDSR IGDLFVGQLK 
SSLTCTDCGY CSTVFDPFWD LSLPIAKRGY PEVTLMDCMR LFTKEDVLDG DEKPTCCRCR 
GRKRCIKKFS IQRFPKILVL HLKRFSESRI RTSKLTTFVN FPLRDLDLRE FASENTNHAV 
YNLYAVSNHS GTTMGGHYTA YCRSPGTGEW HTFNDSSVTP MSSSQVRTSD AYLLFYELAS 
PPSRM