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    TONSL tonsoku like, DNA repair protein [ Homo sapiens (human) ]

    Gene ID: 4796, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TONSLprovided by HGNC
    Official Full Name
    tonsoku like, DNA repair proteinprovided by HGNC
    Primary source
    HGNC:HGNC:7801
    See related
    Ensembl:ENSG00000160949 MIM:604546; AllianceGenome:HGNC:7801
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    IKBR; SEMDSP; NFKBIL2
    Summary
    The protein encoded by this gene is thought to be a negative regulator of NF-kappa-B mediated transcription. The encoded protein may bind NF-kappa-B complexes and trap them in the cytoplasm, preventing them from entering the nucleus and interacting with the DNA. Phosphorylation of this protein targets it for degradation by the ubiquitination pathway, which frees the NF-kappa-B complexes to enter the nucleus. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in bone marrow (RPKM 3.5), small intestine (RPKM 2.3) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TONSL in Genome Data Viewer
    Location:
    8q24.3
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (144428775..144444440, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (145598589..145614253, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (145654158..145669823, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145639267-145640084 Neighboring gene uncharacterized LOC124902041 Neighboring gene solute carrier family 39 member 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145647393-145648164 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145648165-145648934 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:145651263-145652026 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19684 Neighboring gene VPS28 subunit of ESCRT-I Neighboring gene TONSL antisense RNA 1 Neighboring gene microRNA 6893 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145668715-145669223 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19685 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19686 Neighboring gene TMEM276-ZFTRAF1 readthrough Neighboring gene zinc finger TRAF-type containing 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145687825-145688502 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:145688503-145689180 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145689275-145689888 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19689 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19690 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19691 Neighboring gene microRNA 10400 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19692 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145692087-145692923 Neighboring gene transmembrane protein 276 Neighboring gene kinesin family member C2

    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. Cloning of a differentially expressed I kappa B-related protein. Ray P, et al. J Biol Chem, 1995 May 5. PMID 7738005
    2. Novel TONSL variants cause SPONASTRIME dysplasia and associate with spontaneous chromosome breaks, defective cell proliferation and apoptosis. Micale L, et al. Hum Mol Genet, 2020 Nov 4. PMID 32959051
    3. Isolation, sequence, and chromosomal localisation of the human IkappaBR gene (NFKBIL2). Norman DA, et al. Ann Hum Genet, 2000 Jan. PMID 11246458
    4. Oncogenic Impact of TONSL, a Homologous Recombination Repair Protein at the Replication Fork, in Cancer Stem Cells. Lee H, et al. Int J Mol Sci, 2023 May 31. PMID 37298484, Free PMC Article
    5. Common NFKBIL2 polymorphisms and susceptibility to pneumococcal disease: a genetic association study. Chapman SJ, et al. Crit Care, 2010. PMID 21171993, Free PMC Article

    See all (68) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Oncogenic Impact of TONSL, a Homologous Recombination Repair Protein at the Replication Fork, in Cancer Stem Cells.
      Title: Oncogenic Impact of TONSL, a Homologous Recombination Repair Protein at the Replication Fork, in Cancer Stem Cells.
    2. TONSL Is an Immortalizing Oncogene and a Therapeutic Target in Breast Cancer.
      Title: TONSL Is an Immortalizing Oncogene and a Therapeutic Target in Breast Cancer.
    3. MMS22L-TONSL functions in sister chromatid cohesion in a pathway parallel to DSCC1-RFC.
      Title: MMS22L-TONSL functions in sister chromatid cohesion in a pathway parallel to DSCC1-RFC.
    4. Novel TONSL variants cause SPONASTRIME dysplasia and associate with spontaneous chromosome breaks, defective cell proliferation and apoptosis.
      Title: Novel TONSL variants cause SPONASTRIME dysplasia and associate with spontaneous chromosome breaks, defective cell proliferation and apoptosis.
    5. The TONSL promoter is activated by TONSL-AS1. TONSL-AS1 was positively associated with TONSL in cancer tissues. The tumor-inhibiting effect of TONSL-AS1 in gastric cancer cells was associated with TONSL.
      Title: A novel long non-coding RNA TONSL-AS1 regulates progression of gastric cancer via activating TONSL.
    6. Mutations in TONSL Cause SPONASTRIME Dysplasia Phenotype.
      Title: Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia.
    7. Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes.
      Title: Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes.
    8. TONSL holds promise for serving as a prognostic biomarker for hepatocellular carcinoma
      Title: Overexpression of TONSL might be an independent unfavorable prognostic indicator in hepatocellular carcinoma.
    9. uncovered DNA-PKcs-dependent DNA damage-induced ASF1A phosphorylation, which enhances chromatin assembly, promoting MMS22L-TONSL recruitment and, hence, Rad51 loading.
      Title: The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-Mediated Rad51 Loading onto ssDNA during Homologous Recombination in Human Cells.
    10. By specifically regulating RAD51 activity at uncoupled replication forks, MMS22L-TONSL stabilizes perturbed replication forks by promoting replication fork reversal and stimulating their homologous recombination-mediated restart in vivo.
      Title: The MMS22L-TONSL heterodimer directly promotes RAD51-dependent recombination upon replication stress.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    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

    Associated conditions

    Description Tests
    Sponastrime dysplasia
    MedGen: C1300260 OMIM: 271510 GeneReviews: Not available
    		Compare labs

    Variation

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    See Variation Viewer (GRCh37.p13)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ40087

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables histone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables histone reader activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in chromatin organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in double-strand break repair via homologous recombination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in double-strand break repair via homologous recombination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair via homologous recombination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein localization to chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in replication fork processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in replication fork processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in replication fork processing IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of DNA replication factor A complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of FACT complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of MCM complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nuclear body IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nuclear replication fork IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nuclear replication fork IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear replication fork IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in site of double-strand break IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    tonsoku-like protein
    Names
    I-kappa-B-related protein
    NF-kappa-B inhibitor-like protein 2
    ikappaBR
    inhibitor of kappa B-related protein
    nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2

    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_013432.5 → NP_038460.4  tonsoku-like protein

      See identical proteins and their annotated locations for NP_038460.4

      Status: REVIEWED

      Source sequence(s)
      AC084125, AC233992, BC008782, BF475381, CN366457
      Consensus CDS
      CCDS34968.2
      UniProtKB/Swiss-Prot
      B5MDP0, C9JKB1, C9JNV8, Q13006, Q96HA7, Q9UGJ2
      Related
      ENSP00000386239.3, ENST00000409379.8
      Conserved Domains (7) summary
      PHA03247
      Location:668 → 922
      PHA03247; large tegument protein UL36; Provisional
      COG0457
      Location:187 → 418
      TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
      sd00033
      Location:1072 → 1099
      LRR_RI; leucine-rich repeat [structural motif]
      sd00006
      Location:163 → 190
      TPR; TPR repeat [structural motif]
      sd00045
      Location:528 → 559
      ANK; ANK repeat [structural motif]
      pfam12796
      Location:533 → 627
      Ank_2; Ankyrin repeats (3 copies)
      cl42388
      Location:1045 → 1306
      PPP1R42; protein phosphatase 1 regulatory subunit 42

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      144428775..144444440 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011517049.3 → XP_011515351.1  tonsoku-like protein isoform X2

      UniProtKB/TrEMBL
      Q59GI3
      Conserved Domains (8) summary
      cd00116
      Location:709 → 970
      LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
      cd00204
      Location:187 → 299
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      sd00033
      Location:736 → 763
      LRR_RI; leucine-rich repeat [structural motif]
      sd00006
      Location:15 → 45
      TPR; TPR repeat [structural motif]
      pfam12796
      Location:197 → 291
      Ank_2; Ankyrin repeats (3 copies)
      pfam13414
      Location:15 → 88
      TPR_11; TPR repeat
      pfam15671
      Location:371 → 583
      PRR18; Proline-rich protein family 18
      sd00045
      Location:192 → 223
      ANK; ANK repeat [structural motif]

    2. XM_011517048.3 → XP_011515350.1  tonsoku-like protein isoform X1

      UniProtKB/TrEMBL
      Q59GI3
      Conserved Domains (9) summary
      cd00116
      Location:721 → 982
      LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
      cd00204
      Location:199 → 311
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      sd00033
      Location:748 → 775
      LRR_RI; leucine-rich repeat [structural motif]
      sd00006
      Location:27 → 57
      TPR; TPR repeat [structural motif]
      pfam12796
      Location:209 → 303
      Ank_2; Ankyrin repeats (3 copies)
      pfam13414
      Location:27 → 100
      TPR_11; TPR repeat
      pfam13855
      Location:748 → 817
      LRR_8; Leucine rich repeat
      pfam15671
      Location:383 → 595
      PRR18; Proline-rich protein family 18
      sd00045
      Location:204 → 235
      ANK; ANK repeat [structural motif]

    3. XM_011517050.3 → XP_011515352.1  tonsoku-like protein isoform X3

      Conserved Domains (7) summary
      COG0457
      Location:187 → 418
      TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
      cd00204
      Location:523 → 635
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      sd00006
      Location:163 → 190
      TPR; TPR repeat [structural motif]
      pfam12796
      Location:533 → 627
      Ank_2; Ankyrin repeats (3 copies)
      pfam13424
      Location:23 → 99
      TPR_12; Tetratricopeptide repeat
      pfam15671
      Location:707 → 919
      PRR18; Proline-rich protein family 18
      sd00045
      Location:528 → 559
      ANK; ANK repeat [structural motif]

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_018654716.1 Reference GRCh38.p14 PATCHES

      Range
      159377..164883 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      145598589..145614253 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360513.1 → XP_054216488.1  tonsoku-like protein isoform X2

    2. XM_054360512.1 → XP_054216487.1  tonsoku-like protein isoform X1

    3. XM_054360514.1 → XP_054216489.1  tonsoku-like protein isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96HA7.2 GenPept UniProtKB/Swiss-Prot:Q96HA7

    Gene LinkOut

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

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