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    SHFL shiftless antiviral inhibitor of ribosomal frameshifting [ Homo sapiens (human) ]

    Gene ID: 55337, updated on 5-Mar-2024

    Summary

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    Official Symbol
    SHFLprovided by HGNC
    Official Full Name
    shiftless antiviral inhibitor of ribosomal frameshiftingprovided by HGNC
    Primary source
    HGNC:HGNC:25649
    See related
    Ensembl:ENSG00000130813 MIM:616808; AllianceGenome:HGNC:25649
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SFL; IRAV; RyDEN; C19orf66
    Summary
    This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
    Expression
    Ubiquitous expression in liver (RPKM 17.9), spleen (RPKM 17.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SHFL in Genome Data Viewer
    Location:
    19p13.2
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (10086317..10093243)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (10212537..10219461)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (10196993..10203919)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene microRNA 5589 Neighboring gene complement component 3 precursor pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr19:10185500-10185601 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10051 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10052 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10053 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10054 Neighboring gene angiopoietin like 6 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10055 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13936 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13937 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:10216675-10217318 Neighboring gene PPAN-P2RY11 readthrough Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10218607-10219250 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10220162-10220743 Neighboring gene small nucleolar RNA, C/D box 105 Neighboring gene small nucleolar RNA, C/D box 105B Neighboring gene peter pan homolog

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Association of genetic polymorphisms in the C19orf66 gene and biochemical indices of HBV infected individuals in Yunnan. Liu N, et al. Front Cell Infect Microbiol, 2023. PMID 37293200, Free PMC Article
    2. Shiftless Restricts Viral Gene Expression and Influences RNA Granule Formation during Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication. Rodriguez W, et al. J Virol, 2022 Nov 23. PMID 36326276, Free PMC Article
    3. C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein. Yu D, et al. Virol Sin, 2021 Dec. PMID 34309824, Free PMC Article
    4. Modulation of Viral Programmed Ribosomal Frameshifting and Stop Codon Readthrough by the Host Restriction Factor Shiftless. Napthine S, et al. Viruses, 2021 Jun 25. PMID 34202160, Free PMC Article
    5. The SARS-CoV-2 RNA-protein interactome in infected human cells. Schmidt N, et al. Nat Microbiol, 2021 Mar. PMID 33349665, Free PMC Article

    See all (30) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genetic polymorphisms in the C19orf66 gene influenced HIV-1 infection in a Yunnan population.
      Title: Genetic polymorphisms in the C19orf66 gene influenced HIV-1 infection in a Yunnan population.
    2. Association of genetic polymorphisms in the C19orf66 gene and biochemical indices of HBV infected individuals in Yunnan.
      Title: Association of genetic polymorphisms in the C19orf66 gene and biochemical indices of HBV infected individuals in Yunnan.
    3. Shiftless Restricts Viral Gene Expression and Influences RNA Granule Formation during Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.
      Title: Shiftless Restricts Viral Gene Expression and Influences RNA Granule Formation during Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.
    4. C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein.
      Title: C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein.
    5. C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle.
      Title: C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle.
    6. Modulation of Viral Programmed Ribosomal Frameshifting and Stop Codon Readthrough by the Host Restriction Factor Shiftless.
      Title: Modulation of Viral Programmed Ribosomal Frameshifting and Stop Codon Readthrough by the Host Restriction Factor Shiftless.
    7. Taken together, this study identified C19orf66 as a novel interferon-stimulated gene that exerts antiviral effects against Zika virus by specifically degrading th viral NS3 nonstructural protein.
      Title: C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3.
    8. IRAV is an RNA binding protein and localizes to cytoplasmic processing bodies (P bodies) in uninfected cells, where it interacts with the MOV10 RISC complex RNA helicase, suggesting a role for IRAV in the processing of viral RNA.
      Title: IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10.
    9. we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits Dengue virus replication
      Title: Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ11286, FLJ40743

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ribosome binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ribosome binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables sequence-specific mRNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables sequence-specific mRNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in defense response to virus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in defense response to virus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of translational frameshifting IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of viral genome replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of translational termination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to interferon-beta IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to type I interferon IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to type II interferon IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to type III interferon IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in viral translational frameshifting IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in viral translational frameshifting IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in P-body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    shiftless antiviral inhibitor of ribosomal frameshifting protein
    Names
    Repressor of yield of Dengue virus
    UPF0515 protein C19orf66
    interferon-regulated antiviral protein
    repressor of yield of DENV protein
    shiftless

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001308277.2 → NP_001295206.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform 2

      See identical proteins and their annotated locations for NP_001295206.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
      Source sequence(s)
      BC026180, BC035817, DB481173
      Consensus CDS
      CCDS77231.1
      UniProtKB/Swiss-Prot
      Q9NUL5
      Related
      ENSP00000467182.1, ENST00000591813.5
      Conserved Domains (1) summary
      pfam15135
      Location:16 → 232
      UPF0515; Uncharacterized protein UPF0515

    2. NM_018381.4 → NP_060851.2  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform 1

      See identical proteins and their annotated locations for NP_060851.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AK002148, BC010847, DB481173
      Consensus CDS
      CCDS45957.1
      UniProtKB/Swiss-Prot
      A8MQT9, Q4G188, Q8IYH6, Q8N8V1, Q9NUL5
      Related
      ENSP00000253110.10, ENST00000253110.16
      Conserved Domains (1) summary
      pfam15135
      Location:16 → 268
      UPF0515; Uncharacterized protein UPF0515

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      10086317..10093243
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047439048.1 → XP_047295004.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X3

    2. XM_011528122.2 → XP_011526424.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X4

      Conserved Domains (1) summary
      pfam15135
      Location:16 → 78
      UPF0515; Uncharacterized protein UPF0515

    3. XM_047439046.1 → XP_047295002.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X1

    4. XM_047439047.1 → XP_047295003.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X2

      Related
      ENSP00000380978.3, ENST00000397881.7

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      10212537..10219461
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321378.1 → XP_054177353.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X3

    2. XM_054321379.1 → XP_054177354.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X4

    3. XM_054321376.1 → XP_054177351.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X1

    4. XM_054321377.1 → XP_054177352.1  shiftless antiviral inhibitor of ribosomal frameshifting protein isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NUL5.2 GenPept UniProtKB/Swiss-Prot:Q9NUL5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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