Details for: OASL

Gene ID: 8638

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: OASL

Ensembl ID: ENSG00000135114

Description: 2'-5'-oligoadenylate synthetase like

Cell Significance Landscape

Associated with

Significant Cells

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

  • BEST4+ enteroycte CL4030026
    CSI 12.97
    rCSI 16.14%
    PRS 81.07
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 11.34
    rCSI 7.64%
    PRS 91.76
  • non-classical monocyte CL0000875
    CSI 7.31
    rCSI 11.72%
    PRS 90.48
  • foveolar cell of stomach CL0002179
    CSI 6.4
    rCSI 13.62%
    PRS 86.18
  • memory T cell CL0000813
    CSI 4.89
    rCSI 9.42%
    PRS 95.35
  • colon epithelial cell CL0011108
    CSI 3.7
    rCSI 3.88%
    PRS 77.6
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.52
    rCSI 2.53%
    PRS 91.74
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 3.32
    rCSI 6.62%
    PRS 91.1
  • T follicular helper cell CL0002038
    CSI 3.06
    rCSI 2.29%
    PRS 91.87
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 2.99
    rCSI 2.28%
    PRS 91.71
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 2.74
    rCSI 4.68%
    PRS 91.94
  • alpha-beta T cell CL0000789
    CSI 2.7
    rCSI 3.16%
    PRS 92.4
  • mature T cell CL0002419
    CSI 2.67
    rCSI 2.07%
    PRS 92.75
  • CD14-positive monocyte CL0001054
    CSI 2.65
    rCSI 3.3%
    PRS 88.79
  • CD4-positive helper T cell CL0000492
    CSI 2.53
    rCSI 1.91%
    PRS 91.3
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 2.52
    rCSI 3.93%
    PRS 94.53
  • elicited macrophage CL0000861
    CSI 2.42
    rCSI 2.23%
    PRS 87.49
  • goblet cell CL0000160
    CSI 2.35
    rCSI 2.22%
    PRS 78.83
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.24
    rCSI 1.72%
    PRS 83
  • activated type II NK T cell CL0000931
    CSI 2.13
    rCSI 2.4%
    PRS 92.11
  • intestine goblet cell CL0019031
    CSI 2.01
    rCSI 1.79%
    PRS 77.94
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 1.93
    rCSI 2.53%
    PRS 90.21
  • colon goblet cell CL0009039
    CSI 1.9
    rCSI 4.51%
    PRS 85.32
  • mononuclear phagocyte CL0000113
    CSI 1.85
    rCSI 4.06%
    PRS 83.79
  • lung macrophage CL1001603
    CSI 1.85
    rCSI 4.12%
    PRS 86.94
  • neutrophil CL0000775
    CSI 1.82
    rCSI 10.21%
    PRS 81.77
  • alveolar macrophage CL0000583
    CSI 1.47
    rCSI 2.42%
    PRS 83.89
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 1.44
    rCSI 1.72%
    PRS 93.68
  • monocyte CL0000576
    CSI 1.4
    rCSI 2.54%
    PRS 85.16
  • alternatively activated macrophage CL0000890
    CSI 1.37
    rCSI 1.72%
    PRS 88.93
  • small intestine goblet cell CL1000495
    CSI 1.31
    rCSI 2.88%
    PRS 85.63
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.28
    rCSI 3.46%
    PRS 84.81
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.21
    rCSI 3.48%
    PRS 94.83
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.01
    rCSI 1.22%
    PRS 61.25
  • intermediate monocyte CL0002393
    CSI 0.88
    rCSI 1.33%
    PRS 85.25
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.37
    rCSI 1.84%
    PRS 90.97
  • epithelial cell of urethra CL1000296
    CSI 0.24
    rCSI 5.94%
    PRS 87.67

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 [OASL](/details-gene/8638) (2'-5'-Oligoadenylate Synthetase Like) is a protein-coding gene located on chromosome 12q24.31. It belongs to the OAS family of interferon-stimulated proteins that play a central role in innate immunity. The encoded protein is a key effector in the host's antiviral defense system, participating in pathways that detect viral components and restrict viral replication. Consistent with its function as an interferon-stimulated gene, [OASL](/details-gene/8638) shows significant expression across a wide range of immune cell subsets, particularly memory T cells and monocytes. Interestingly, its highest significance is observed in specialized epithelial cells of the gastrointestinal tract, such as [BEST4+ enteroycte](/details-cell/CL4030026), suggesting a crucial role in mucosal barrier defense against pathogens. ## Cellular Roles and Expression Landscape The expression profile of [OASL](/details-gene/8638) highlights its dual importance in both the immune system and at epithelial barriers. **Overall**, the gene's most significant expression is in [BEST4+ enteroycte](/details-cell/CL4030026) (CSI: 12.97), a specialized intestinal epithelial cell, and [foveolar cell of stomach](/details-cell/CL0002179) (CSI: 6.40), pointing towards a specialized function in innate immunity at mucosal surfaces. Beyond the gastrointestinal epithelium, [OASL](/details-gene/8638) is a prominent marker across multiple immune lineages, indicating a broad role in systemic host defense. It is highly significant in the T cell compartment, particularly within memory subsets such as the [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907) (CSI: 11.34) and [memory T cell](/details-cell/CL0000813) (CSI: 4.89). Its significance extends to effector T cells and helper subsets, including [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) and [CD4-positive helper T cell](/details-cell/CL0000492), consistent with a function in executing adaptive antiviral responses. In the myeloid lineage, [OASL](/details-gene/8638) is a key feature of monocytes, showing high significance in [non-classical monocyte](/details-cell/CL0000875) (CSI: 7.31) and [CD14-positive monocyte](/details-cell/CL0001054) (CSI: 2.65). This expression pattern suggests that [OASL](/details-gene/8638) is a core component of the immediate innate response to pathogens initiated by these sentinel cells. ## Pathways and Molecular Function Functionally, [OASL](/details-gene/8638) is deeply integrated into the interferon (IFN)-mediated antiviral response. As annotated by Reactome, it is a key component of the '[Antiviral mechanism by ifn-stimulated genes](/details-gene/R-HSA-1169410)', playing a role in both '[Interferon alpha/beta signaling](/details-gene/R-HSA-909733)' and '[Interferon gamma signaling](/details-gene/R-HSA-877300)'. This is corroborated by Gene Ontology annotations, which place it centrally in the '[Antiviral innate immune response](/details-gene/GO:0140374)' and the '[Defense response to virus](/details-gene/GO:0051607)'. At the molecular level, [OASL](/details-gene/8638) is known to bind double-stranded RNA ([GO:0003725](/details-gene/GO:0003725)), a common molecular pattern associated with viral replication. This binding is believed to trigger downstream signaling events. While it belongs to the 2'-5'-oligoadenylate synthetase family, some studies suggest the human [OASL](/details-gene/8638) protein lacks canonical enzymatic activity ([Link](https://doi.org/10.1093/nar/26.18.4121)). Instead, its antiviral function appears to be mediated through protein-protein interactions, possibly by amplifying pattern recognition receptor signaling pathways, such as the '[Positive regulation of rig-i signaling pathway](/details-gene/GO:1900246)'. This suggests it functions as a signaling scaffold or amplifier to potentiate the innate immune response upon viral detection ([Link](https://doi.org/10.1099/vir.0.2008/003558-0)). The gene's involvement in these pathways is highly consistent with its expression in immune cells and barrier epithelial cells, which are primary sites of viral encounters. ## Research Directions The unique expression pattern and known functions of [OASL](/details-gene/8638) suggest several avenues for future investigation. Its role as an interferon-stimulated gene is well-established, but its specific contribution within distinct cellular contexts remains an area of active research. **Proposed Hypotheses:** 1. Given its top-ranking CSI in [BEST4+ enteroycte](/details-cell/CL4030026), [OASL](/details-gene/8638) may function as a critical, cell-intrinsic gatekeeper against enteric viruses. We hypothesize that [OASL](/details-gene/8638) acts as a primary sensor or signal amplifier in these specialized gut epithelial cells, initiating localized antiviral programs to prevent viral dissemination from the intestinal lumen. 2. The high significance of [OASL](/details-gene/8638) in [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907)s suggests a role beyond immediate antiviral defense. We hypothesize that constitutive or IFN-induced [OASL](/details-gene/8638) expression in memory T cells maintains them in a state of "antiviral readiness," lowering the threshold for reactivation and rapid deployment of effector functions upon secondary viral exposure. **Experimental Approach:** To test the first hypothesis, one could utilize human intestinal organoids differentiated to contain [BEST4+ enteroycte](/details-cell/CL4030026)s. Using CRISPR-Cas9, [OASL](/details-gene/8638) would be knocked out in these organoids. Control and knockout organoids would then be infected with a relevant enteric virus, such as norovirus or rotavirus. The impact of [OASL](/details-gene/8638) deletion would be assessed by quantifying viral replication (via qPCR for viral genomes or plaque assays), measuring the induction of other key antiviral genes (e.g., *IFNB1*, *ISG15*) via RNA-seq, and monitoring epithelial barrier integrity. A significant increase in viral replication and a blunted interferon response in knockout organoids would support the hypothesis. **Therapeutic Potential:** As an intracellular protein central to host-directed immunity, [OASL](/details-gene/8638) presents an intriguing but challenging therapeutic target. Direct inhibition would be counterproductive for treating infections. Instead, strategies aimed at **activation** or potentiation of its function could be beneficial. The development of small molecules that stabilize the [OASL](/details-gene/8638) protein or enhance its ability to amplify RIG-I signaling could represent a novel, host-directed antiviral therapy. Such an agent could act as a broad-spectrum antiviral by boosting the intrinsic defense mechanisms of infected cells, offering an alternative or complement to pathogen-specific drugs.

Genular Protein ID: 3269379460

Symbol: OASL_HUMAN

Name: 2'-5'-oligoadenylate synthase-like protein

UniProtKB Accession Codes:

Q15646 B2RAZ2 I1YDD2 O75686 Q17R95 Q9Y6K6 Q9Y6K7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 16 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 3 RefSeq 4 SMART 1 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9722630

Title: p59OASL, a 2'-5' oligoadenylate synthetase like protein: a novel human gene related to the 2'-5' oligoadenylate synthetase family.

PubMed ID: 9722630

DOI: 10.1093/nar/26.18.4121

PubMed ID: 9826176

Title: Molecular cloning and characterization of two related and interferon-induced 56-kDa and 30-kDa proteins highly similar to 2'-5' oligoadenylate synthetase.

PubMed ID: 9826176

DOI: 10.1046/j.1432-1327.1998.2570319.x

PubMed ID: 22531715

Title: Identification of OASL d, a splice variant of human OASL, with antiviral activity.

PubMed ID: 22531715

DOI: 10.1016/j.biocel.2012.04.001

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 7776974

Title: Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor.

PubMed ID: 7776974

DOI: 10.1210/mend.9.2.7776974

PubMed ID: 14728690

Title: Interaction between the 2'-5' oligoadenylate synthetase-like protein p59 OASL and the transcriptional repressor methyl CpG-binding protein 1.

PubMed ID: 14728690

DOI: 10.1046/j.1432-1033.2003.03966.x

PubMed ID: 17408844

Title: The human 2'-5'oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation.

PubMed ID: 17408844

DOI: 10.1016/j.biochi.2007.02.003

PubMed ID: 18931074

Title: The p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the C-terminal ubiquitin-like domain.

PubMed ID: 18931074

DOI: 10.1099/vir.0.2008/003558-0

PubMed ID: 19203244

Title: Differential regulation of the OASL and OAS1 genes in response to viral infections.

PubMed ID: 19203244

DOI: 10.1089/jir.2008.0050

PubMed ID: 19904482

Title: Evolution of the 2'-5'-oligoadenylate synthetase family in eukaryotes and bacteria.

PubMed ID: 19904482

DOI: 10.1007/s00239-009-9299-1

PubMed ID: 20074559

Title: 2',5'-Oligoadenylate synthetase-like gene highly induced by hepatitis C virus infection in human liver is inhibitory to viral replication in vitro.

PubMed ID: 20074559

DOI: 10.1016/j.bbrc.2010.01.034

PubMed ID: 21142819

Title: The oligoadenylate synthetase family: an ancient protein family with multiple antiviral activities.

PubMed ID: 21142819

DOI: 10.1089/jir.2010.0107

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

Sequence Information:

  • Length: 514
  • Mass: 59226
  • Checksum: 4D8BB655D9EA003E
  • Sequence:
    • MALMQELYST PASRLDSFVA QWLQPHREWK EEVLDAVRTV EEFLRQEHFQ GKRGLDQDVR 
VLKVVKVGSF GNGTVLRSTR EVELVAFLSC FHSFQEAAKH HKDVLRLIWK TMWQSQDLLD 
LGLEDLRMEQ RVPDALVFTI QTRGTAEPIT VTIVPAYRAL GPSLPNSQPP PEVYVSLIKA 
CGGPGNFCPS FSELQRNFVK HRPTKLKSLL RLVKHWYQQY VKARSPRANL PPLYALELLT 
IYAWEMGTEE DENFMLDEGF TTVMDLLLEY EVICIYWTKY YTLHNAIIED CVRKQLKKER 
PIILDPADPT LNVAEGYRWD IVAQRASQCL KQDCCYDNRE NPISSWNVKR ARDIHLTVEQ 
RGYPDFNLIV NPYEPIRKVK EKIRRTRGYS GLQRLSFQVP GSERQLLSSR CSLAKYGIFS 
HTHIYLLETI PSEIQVFVKN PDGGSYAYAI NPNSFILGLK QQIEDQQGLP KKQQQLEFQG 
QVLQDWLGLG IYGIQDSDTL ILSKKKGEAL FPAS