Details for: UBR7

Gene ID: 55148

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: UBR7

Ensembl ID: ENSG00000012963

Description: ubiquitin protein ligase E3 component n-recognin 7

Cell Significance Landscape

Associated with

Significant Cells

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

  • neural progenitor cell CL0011020
    CSI 5.48
    rCSI 24.11%
    PRS 84.82
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 4.38
    rCSI 3.33%
    PRS 98.83
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.93
    rCSI 2.05%
    PRS 96.18
  • pro-B cell CL0000826
    CSI 2.92
    rCSI 2.42%
    PRS 94.68
  • common myeloid progenitor CL0000049
    CSI 2.91
    rCSI 2.35%
    PRS 94.73
  • neural crest cell CL0011012
    CSI 2.89
    rCSI 2.28%
    PRS 88.89
  • multi-ciliated epithelial cell CL0005012
    CSI 2.65
    rCSI 2.64%
    PRS 89.25
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.55
    rCSI 2.94%
    PRS 87.63
  • Mueller cell CL0000636
    CSI 2.48
    rCSI 5.66%
    PRS 88.83
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.35
    rCSI 3.03%
    PRS 85.39
  • retinal rod cell CL0000604
    CSI 2.26
    rCSI 3.98%
    PRS 90.53
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.2
    rCSI 2.74%
    PRS 82.36
  • epithelial cell CL0000066
    CSI 2.11
    rCSI 3.24%
    PRS 83.4
  • mesenchymal cell CL0008019
    CSI 1.72
    rCSI 4.36%
    PRS 90.2
  • amacrine cell CL0000561
    CSI 1.64
    rCSI 4.75%
    PRS 87.44
  • retinal cone cell CL0000573
    CSI 1.58
    rCSI 2.54%
    PRS 87.57
  • cytotoxic T cell CL0000910
    CSI 1.42
    rCSI 8.14%
    PRS 91.82
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.42
    rCSI 2.5%
    PRS 83.87
  • promonocyte CL0000559
    CSI 1.26
    rCSI 2.15%
    PRS 95.07
  • large pre-B-II cell CL0000957
    CSI 1.15
    rCSI 3.28%
    PRS 93.17
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.02
    rCSI 2.49%
    PRS 82.4
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.02
    rCSI 3.19%
    PRS 85.45
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 0.9
    rCSI 1.09%
    PRS 76.6
  • primitive red blood cell CL0002355
    CSI 0.87
    rCSI 4.68%
    PRS 94.35
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.59
    rCSI 2.12%
    PRS 82.69
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.28
    rCSI 6.87%
    PRS 82.17
  • direct pathway medium spiny neuron CL4023026
    CSI 0.25
    rCSI 5.92%
    PRS 82.24

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)

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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 [UBR7](/details-gene/55148) is a protein-coding gene located on chromosome 14q32.12 that encodes the Ubiquitin Protein Ligase E3 Component N-Recognin 7. As a putative E3 ubiquitin-protein ligase, it plays a fundamental role in the post-translational modification of proteins by tagging them for degradation or altering their function. **Overall**, expression data reveals that [UBR7](/details-gene/55148) has a high cellular significance in a diverse array of cell types, most notably in [neural progenitor cell](/details-cell/CL0011020) (CSI: 5.48) and [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) (CSI: 4.38). This broad yet distinct expression pattern suggests its involvement in both nervous system development and adaptive immune responses. Its function in neurodevelopment is supported by research linking it to the Notch signaling pathway and a specific neurodevelopmental syndrome characterized by epilepsy and other anomalies [Link](https://doi.org/10.1016/j.ajhg.2020.11.018). ## Cellular Roles and Expression Landscape The expression profile of [UBR7](/details-gene/55148) indicates a multifaceted role across various lineages, with a pronounced significance in both the central nervous system and the hematopoietic system. **Overall**, its highest significance is observed in [neural progenitor cell](/details-cell/CL0011020), with high scores also noted in related cell types such as [neural crest cell](/details-cell/CL0011012) and [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338). This pattern strongly suggests a critical function during neurogenesis and neural differentiation. Concurrently, [UBR7](/details-gene/55148) exhibits high significance in several key immune cell populations. It is a prominent marker in [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050), [plasmacytoid dendritic cell, human](/details-cell/CL0001058), and hematopoietic precursors like the [pro-B cell](/details-cell/CL0000826) and [common myeloid progenitor](/details-cell/CL0000049). This expression pattern points towards a role in immune cell development and the execution of effector functions, particularly within the adaptive immune system. The gene's activity is not restricted to undifferentiated cells, as it is also significant in terminally differentiated cells such as [retinal rod cell](/details-cell/CL0000604) and various GABAergic interneurons, highlighting a sustained role in cellular maintenance and function. ## Pathways and Molecular Function Functionally, [UBR7](/details-gene/55148) is annotated with [ubiquitin protein ligase activity](/details-go/GO:0061630) and is a key component of the [protein ubiquitination](/details-go/GO:0016567) machinery. This molecular function allows it to mediate the attachment of ubiquitin to substrate proteins, a process that can lead to their degradation by the proteasome or modulate their activity, localization, or interaction partners. The protein also possesses [zinc ion binding](/details-go/GO:0008270) capabilities, characteristic of many E3 ligases containing a RING-finger domain, which is essential for its catalytic activity. Recent studies have placed [UBR7](/details-gene/55148) as a functional component of the Notch signaling pathway, a highly conserved cell-cell communication system critical for embryonic development, particularly neurogenesis [Link](https://doi.org/10.1016/j.ajhg.2020.11.018). This finding provides a direct molecular link between its E3 ligase activity and its high expression in [neural progenitor cell](/details-cell/CL0011020), where precise regulation of Notch signaling is paramount for controlling cell fate decisions between proliferation and differentiation. ## Research Directions The dual prominence of [UBR7](/details-gene/55148) in both neurodevelopment and mature immune cell function presents several avenues for future research. While its role in neurodevelopment is beginning to be elucidated, its function in the immune system, particularly in cytotoxic T cells, remains largely unexplored. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** [UBR7](/details-gene/55148) is a critical regulator of neural progenitor cell fate decisions by ubiquitinating and promoting the turnover of key repressors of neuronal differentiation within the Notch signaling pathway. Dysregulation of this process may lead to the developmental defects observed in associated syndromes. 2. **Hypothesis 2:** In [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050), [UBR7](/details-gene/55148) controls the magnitude and duration of the cytotoxic response by regulating the stability of key effector molecules, such as granzymes or perforin, or transcription factors that drive their expression. A potential experimental approach to test the first hypothesis would be to use a CRISPR-Cas9 knockout or dCas9-KRAB-mediated knockdown of [UBR7](/details-gene/55148) in a human induced pluripotent stem cell (iPSC) model of neurogenesis. Differentiating these modified iPSCs into neural rosettes and subsequently into mature neurons would allow for detailed characterization. Changes in differentiation efficiency and neuronal subtype specification could be quantified using single-cell RNA sequencing and immunofluorescence for lineage markers. Concurrently, tandem mass tag (TMT) proteomics could identify specific proteins that are differentially ubiquitinated in the absence of [UBR7](/details-gene/55148) function, thereby revealing its direct substrates. As a therapeutic target, [UBR7](/details-gene/55148) presents significant challenges. Given its broad expression and fundamental role in protein turnover, systemic inhibition would likely cause severe toxicity. However, for monogenic neurodevelopmental disorders caused by loss-of-function mutations, strategies aimed at restoring its function or modulating the activity of its downstream targets could be explored. Its role as an E3 ligase makes it a difficult target for small molecule activators, but therapies focused on compensating for the dysregulation of its specific, disease-relevant substrates may offer a more tractable path forward.

Genular Protein ID: 1076172370

Symbol: UBR7_HUMAN

Name: Putative E3 ubiquitin-protein ligase UBR7

UniProtKB Accession Codes:

Q8N806 Q86U21 Q86UA9 Q96BY0 Q9NVV6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMART 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 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: 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: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24664117

Title: Identification and characterization of RING-finger ubiquitin ligase UBR7 in mammalian spermatozoa.

PubMed ID: 24664117

DOI: 10.1007/s00441-014-1808-x

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 33340455

Title: UBR7 functions with UBR5 in the Notch signaling pathway and is involved in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism.

PubMed ID: 33340455

DOI: 10.1016/j.ajhg.2020.11.018

Sequence Information:

  • Length: 425
  • Mass: 47999
  • Checksum: 6FFE5795E6737BE5
  • Sequence:
    • MAGAEGAAGR QSELEPVVSL VDVLEEDEEL ENEACAVLGG SDSEKCSYSQ GSVKRQALYA 
CSTCTPEGEE PAGICLACSY ECHGSHKLFE LYTKRNFRCD CGNSKFKNLE CKLLPDKAKV 
NSGNKYNDNF FGLYCICKRP YPDPEDEIPD EMIQCVVCED WFHGRHLGAI PPESGDFQEM 
VCQACMKRCS FLWAYAAQLA VTKISTEDDG LVRNIDGIGD QEVIKPENGE HQDSTLKEDV 
PEQGKDDVRE VKVEQNSEPC AGSSSESDLQ TVFKNESLNA ESKSGCKLQE LKAKQLIKKD 
TATYWPLNWR SKLCTCQDCM KMYGDLDVLF LTDEYDTVLA YENKGKIAQA TDRSDPLMDT 
LSSMNRVQQV ELICEYNDLK TELKDYLKRF ADEGTVVKRE DIQQFFEEFQ SKKRRRVDGM 
QYYCS