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Domain

The ANK repeats mediate the interaction with the MCM complex and histones, while the LRR repeats mediate the interaction with MMS22L.

Function

Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks (PubMed:21055983, PubMed:21055984, PubMed:21055985, PubMed:21113133, PubMed:26527279, PubMed:27338793, PubMed:27797818, PubMed:29478807, PubMed:30773278). The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication (PubMed:21055983, PubMed:21055984, PubMed:21055985). It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs (PubMed:21055983, PubMed:21055984, PubMed:21055985, PubMed:27797818, PubMed:29478807). Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination (PubMed:27797818, PubMed:29478807). Within the complex, TONSL acts as a histone reader, which recognizes and binds newly synthesized histones following their replacement by histone chaperones (PubMed:27338793, PubMed:29478807). Specifically binds histone H4 lacking methylation at 'Lys-20' (H4K20me0) and histone H3.1 (PubMed:27338793).

Involvement in disease

Spondyloepimetaphyseal dysplasia, sponastrime type

SEMDSP

An autosomal recessive bone disease characterized by spine abnormalities, mid-face hypoplasia with a depressed nasal bridge, and striation of the metaphyses. Additional features include disproportionate short stature with exaggerated lumbar lordosis, scoliosis, coxa vara, limited elbow extension, small dysplastic epiphyses, childhood cataracts, short dental roots, and hypogammaglobulinemia. Disease severity and clinical manifestations are variable. Some patients have intellectual disability.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence similarities

Belongs to the Tonsoku family.

Tissue specificity

Expressed in heart, skeletal muscle and tracheal epithelial cells.

Cellular localization

  • Nucleus
  • Chromosome
  • Cytoplasm
  • Mainly nuclear (PubMed:21055983, PubMed:21055984). Localizes to DNA damage sites, accumulates at stressed replication forks (PubMed:21055983, PubMed:21055984, PubMed:26527279, PubMed:27338793). Recruited to stalled or collapsed replication forks following histone replacement by histone chaperones ASF1A and the CAF-1 complex: TONSL acts as a histone reader that recognizes and binds newly synthesized histones (PubMed:29478807).

Alternative names

IKBR, NFKBIL2, TONSL, Tonsoku-like protein, Inhibitor of kappa B-related protein, NF-kappa-B inhibitor-like protein 2, Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2, I-kappa-B-related protein, IkappaBR

Target type

Proteins

Molecular weight

150929Da

We found 1 product in 1 category

Primary Antibodies

Target

Application

Reactive species

Search our catalogue for 'NFKBIL2' (1)

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