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

Summary

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

Location:: 8q24.3

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (144428775..144444440, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (145598589..145614253, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (145654158..145669823, complement)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
Mutations in TONSL Cause SPONASTRIME Dysplasia Phenotype.
Title: Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia.
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.
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.
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.
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 variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

sY3084 (e-PCR)
- UniSTS:515126

L18426 (e-PCR)
- UniSTS:34648

D11S3114 (e-PCR)
- UniSTS:152207

RH71203 (e-PCR)
- UniSTS:9631

L17971 (e-PCR)
- UniSTS:43966

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)

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

144428775..144444440 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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]
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]