Details for: DNASE2B

Gene ID: 58511

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: DNASE2B

Ensembl ID: ENSG00000137976

Description: deoxyribonuclease 2 beta

Cell Significance Landscape

Associated with

Significant Cells

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

  • alveolar macrophage CL0000583
    CSI 2.48
    rCSI 4.08%
    PRS 99.92

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 [DNASE2B](/details-gene/58511), or deoxyribonuclease 2 beta, is a protein-coding gene located on chromosome 1. It encodes an acid deoxyribonuclease that is functionally implicated in the degradation of DNA, particularly during [apoptotic dna fragmentation](/details-go/GO:0006309) ([Link](https://doi.org/10.1016/s0378-1119(01)00434-6)). The enzyme exhibits [deoxyribonuclease ii activity](/details-go/GO:0004531) and is localized to the [lysosome](/details-go/GO:0005764) and the [extracellular region](/details-go/GO:0005576). Expression data indicates that [DNASE2B](/details-gene/58511) is a highly specific marker for [alveolar macrophage](/details-cell/CL0000583), suggesting a specialized role in the innate immune system of the lung. ## Cellular Roles and Expression Landscape The expression profile of [DNASE2B](/details-gene/58511) points towards a highly specialized function within the pulmonary immune system. **Overall**, the gene shows its most significant expression in the [alveolar macrophage](/details-cell/CL0000583) (CSI: 2.48). This high specificity suggests that [DNASE2B](/details-gene/58511) is not a general housekeeping gene but rather a key functional component of this particular cell type. Alveolar macrophages are phagocytic cells responsible for clearing cellular debris, pathogens, and inhaled particles from the lung's airspaces. The prominent expression of a DNA-degrading enzyme in these cells is consistent with a critical role in processing the DNA from ingested apoptotic bodies, bacteria, and viruses, thereby maintaining lung homeostasis and preventing aberrant inflammation. ## Pathways and Molecular Function The functional annotations for [DNASE2B](/details-gene/58511) align closely with its cellular expression pattern. Its primary molecular function is categorized as [deoxyribonuclease ii activity](/details-go/GO:0004531), which is the hydrolysis of DNA in an acidic environment, characteristic of the lysosome. This is directly linked to its involvement in the biological process of [apoptotic dna fragmentation](/details-go/GO:0006309). The dual localization of the [DNASE2B](/details-gene/58511) protein to both the [lysosome](/details-go/GO:0005764) and the [extracellular region](/details-go/GO:0005576) suggests two distinct but complementary roles. Intracellularly, it likely functions within the phagolysosomes of [alveolar macrophage](/details-cell/CL0000583) to degrade DNA from engulfed material. Extracellularly, it may serve to break down DNA present in the alveolar space, such as that released from necrotic cells or in Neutrophil Extracellular Traps (NETs), which can otherwise promote inflammation and tissue damage if not properly cleared. ## Research Directions The highly specific expression of [DNASE2B](/details-gene/58511) in [alveolar macrophage](/details-cell/CL0000583) positions it as a gene of interest for lung physiology and pathology. While comparative data across different health and disease contexts are not provided, its function suggests its dysregulation could be a factor in inflammatory lung diseases. **Proposed Hypotheses:** 1. [DNASE2B](/details-gene/58511) is essential for the non-inflammatory clearance of DNA-containing debris by [alveolar macrophage](/details-cell/CL0000583). Its deficiency could lead to the accumulation of self-DNA, triggering TLR9-mediated inflammatory pathways and contributing to the pathogenesis of diseases like acute lung injury or pulmonary fibrosis. 2. The extracellular activity of [DNASE2B](/details-gene/58511) is critical for dismantling Neutrophil Extracellular Traps (NETs) in the lungs. In conditions with excessive neutrophilic inflammation, such as severe pneumonia or Acute Respiratory Distress Syndrome (ARDS), insufficient [DNASE2B](/details-gene/58511) activity may result in persistent NETs, leading to prolonged inflammation and lung damage. **Key Experimental Approach:** To test the hypothesis that [DNASE2B](/details-gene/58511) is critical for preventing DNA-driven inflammation in the lung, a compelling experiment would involve a conditional knockout mouse model. Specifically, one could generate mice with a floxed *Dnase2b* allele and cross them with mice expressing Cre recombinase under an alveolar macrophage-specific promoter (e.g., *Itgax*-Cre). These knockout mice and their wild-type littermates would then be challenged with an intratracheal administration of apoptotic cells or a viral pathogen like influenza. Bronchoalveolar lavage (BAL) fluid and lung tissue would be analyzed at various time points to quantify the clearance of apoptotic debris, measure levels of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6), and assess the activation of innate immune signaling pathways using RNA-seq on sorted alveolar macrophages. **Therapeutic Potential:** Given its role as an enzyme that degrades potentially pro-inflammatory material, [DNASE2B](/details-gene/58511) represents a potential therapeutic agent where **activation** or supplementation would be the desired strategy. Its function is analogous to DNase I (dornase alfa), which is used to treat cystic fibrosis by degrading viscous extracellular DNA in mucus. Therefore, recombinant human [DNASE2B](/details-gene/58511), perhaps engineered for greater stability and delivered via inhalation, could be a promising therapy for a range of pulmonary diseases characterized by high cell turnover and DNA accumulation, including ARDS, COPD, and severe viral pneumonias. Its specificity for the acidic environment of the lysosome or inflamed tissues could offer a targeted effect with fewer systemic side effects.

Genular Protein ID: 730137357

Symbol: DNS2B_HUMAN

Name: Deoxyribonuclease-2-beta

UniProtKB Accession Codes:

Q8WZ79 Q5VXD0 Q5VXD1 Q8WZ80 Q9NQW3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 6 Ensembl 2 GO 4 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 3 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11700027

Title: Isolation and characterization of the DLAD/Dlad genes, which lie head-to-head with the genes for urate oxidase.

PubMed ID: 11700027

DOI: 10.1006/bbrc.2001.5894

PubMed ID: 11376952

Title: The cloning, genomic structure, localization, and expression of human deoxyribonuclease IIbeta.

PubMed ID: 11376952

DOI: 10.1016/s0378-1119(01)00434-6

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 12944971

Title: Nuclear cataract caused by a lack of DNA degradation in the mouse eye lens.

PubMed ID: 12944971

DOI: 10.1038/nature01895

Sequence Information:

  • Length: 361
  • Mass: 41713
  • Checksum: C6FDD3F58F62CAC0
  • Sequence:
    • MKQKMMARLL RTSFALLFLG LFGVLGAATI SCRNEEGKAV DWFTFYKLPK RQNKESGETG 
LEYLYLDSTT RSWRKSEQLM NDTKSVLGRT LQQLYEAYAS KSNNTAYLIY NDGVPKPVNY 
SRKYGHTKGL LLWNRVQGFW LIHSIPQFPP IPEEGYDYPP TGRRNGQSGI CITFKYNQYE 
AIDSQLLVCN PNVYSCSIPA TFHQELIHMP QLCTRASSSE IPGRLLTTLQ SAQGQKFLHF 
AKSDSFLDDI FAAWMAQRLK THLLTETWQR KRQELPSNCS LPYHVYNIKA IKLSRHSYFS 
SYQDHAKWCI SQKGTKNRWT CIGDLNRSPH QAFRSGGFIC TQNWQIYQAF QGLVLYYESC 
K

Genular Protein ID: 1011395480

Symbol: Q66K39_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q66K39

Database IDs:

ARBA 4 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 3 InterPro 1 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 1 RuleBase 1

Citations:

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

Sequence Information:

  • Length: 251
  • Mass: 29034
  • Checksum: DE8BB7C35757BCA1
  • Sequence:
    • NDGVPKPVNY SRKYGHTKGL LLWNRVQGFW LIHSIPQFPP IPEEGYDYPP TGRRNGQSGI 
CITFKYNQYE AIDSQLLVCN PNVYSCSIPA TFHQELIHMP QLCTRASSSE IPGRLLTTLQ 
SAQGQKFLHF AKSDSFLDDI FAAWMAQRLK THLLTETWQR KRQELPSNCS LPYHVYNIKA 
IKLSRHSYFS SYQDHAKWCI SQKGTKNRWT CIGDLNRSPH QAFRSGGFIC TQNWQIYQAF 
QGLVLYYESC K