TONSL
entrez
4796
canonical
uniprot
Q96HA7
canonical
ensembl
ENSG00000160949
resolver
ensp
ENSP00000386239
resolver
ensp
ENSP00000738006
resolver
genesymbol
TONSL
resolver
genesymbol_syn
IKBR
resolver
genesymbol_syn
NFKBIL2
resolver
hgnc
HGNC:7801
resolver
uniprot
B5MDP0
resolver
uniprot
C9JKB1
resolver
uniprot
C9JNV8
resolver
uniprot
Q13006
resolver
uniprot
Q9UGJ2
resolver
uniprot_entry
TONSL_HUMAN
resolver
uniprot_sec
B5MDP0
resolver
uniprot_sec
C9JKB1
resolver
uniprot_sec
C9JNV8
resolver
uniprot_sec
Q13006
resolver
uniprot_sec
Q9UGJ2
resolver
amino_acid_sequence
MSLERELRQLSKAKAKAQRAGQRREEAALCHQLGELLAGHGRYAEALEQHWQELQLRERADDPLGCAVAHRKIGERLAEMEDYPAALQHQHQYLELAHSLRNHTELQRAWATIGRTHLDIYDHCQSRDALLQAQAAFEKSLAIVDEELEGTLAQGELNEMRTRLYLNLGLTFESLQQTALCNDYFRKSIFLAEQNHLYEDLFRARYNLGTIHWRAGQHSQAMRCLEGARECAHTMRKRFMESECCVVIAQVLQDLGDFLAAKRALKKAYRLGSQKPVQRAAICQNLQHVLAVVRLQQQLEEAEGRDPQGAMVICEQLGDLFSKAGDFPRAAEAYQKQLRFAELLDRPGAERAIIHVSLATTLGDMKDHHGAVRHYEEELRLRSGNVLEEAKTWLNIALSREEAGDAYELLAPCFQKALSCAQQAQRPQLQRQVLQHLHTVQLRLQPQEAPETETRLRELSVAEDEDEEEEAEEAAATAESEALEAGEVELSEGEDDTDGLTPQLEEDEELQGHLGRRKGSKWNRRNDMGETLLHRACIEGQLRRVQDLVRQGHPLNPRDYCGWTPLHEACNYGHLEIVRFLLDHGAAVDDPGGQGCEGITPLHDALNCGHFEVAELLLERGASVTLRTRKGLSPLETLQQWVKLYRRDLDLETRQKARAMEMLLQAAASGQDPHSSQAFHTPSSLLFDPETSPPLSPCPEPPSNSTRLPEASQAHVRVSPGQAAPAMARPRRSRHGPASSSSSSEGEDSAGPARPSQKRPRCSATAQRVAAWTPGPASNREAATASTSRAAYQAAIRGVGSAQSRLGPGPPRGHSKALAPQAALIPEEECLAGDWLELDMPLTRSRRPRPRGTGDNRRPSSTSGSDSEESRPRARAKQVRLTCMQSCSAPVNAGPSSLASEPPGSPSTPRVSEPSGDSSAAGQPLGPAPPPPIRVRVQVQDHLFLIPVPHSSDTHSVAWLAEQAAQRYYQTCGLLPRLTLRKEGALLAPQDLIPDVLQSNDEVLAEVTSWDLPPLTDRYRRACQSLGQGEHQQVLQAVELQGLGLSFSACSLALDQAQLTPLLRALKLHTALRELRLAGNRLGDKCVAELVAALGTMPSLALLDLSSNHLGPEGLRQLAMGLPGQATLQSLEELDLSMNPLGDGCGQSLASLLHACPLLSTLRLQACGFGPSFFLSHQTALGSAFQDAEHLKTLSLSYNALGAPALARTLQSLPAGTLLHLELSSVAAGKGDSDLMEPVFRYLAKEGCALAHLTLSANHLGDKAVRDLCRCLSLCPSLISLDLSANPEISCASLEELLSTLQKRPQGLSFLGLSGCAVQGPLGLGLWDKIAAQLRELQLCSRRLCAEDRDALRQLQPSRPGPGECTLDHGSKLFFRRL
uniprot
proteins
disease_involvement
DISEASE: Spondyloepimetaphyseal dysplasia, sponastrime type (SEMDSP) [MIM:271510]: 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. {ECO:0000269|PubMed:30773277, ECO:0000269|PubMed:30773278, ECO:0000269|PubMed:32959051}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {ECO:0000269|PubMed:21055983, ECO:0000269|PubMed:21055984, ECO:0000269|PubMed:21055985, ECO:0000269|PubMed:21113133, ECO:0000269|PubMed:26527279, ECO:0000269|PubMed:27338793, ECO:0000269|PubMed:27797818, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30773278}.
uniprot
proteins
mass_dalton
150929
uniprot
proteins
mutagenesis
MUTAGEN 530; /note="E->A: Abolished interaction with histone H4 and recruitment to replication forks without affecting interaction with MMS22L."; /evidence="ECO:0000269|PubMed:27338793"; MUTAGEN 559; /note="D->A: Abolished interaction with histone H4 and recruitment to replication forks without affecting interaction with MMS22L."; /evidence="ECO:0000269|PubMed:27338793"; MUTAGEN 563; /note="W->A: Abolished interaction with histone H4 and recruitment to replication forks without affecting interaction with MMS22L."; /evidence="ECO:0000269|PubMed:27338793"; MUTAGEN 568; /note="E->A: Abolished interaction with histone H4 and recruitment to replication forks without affecting interaction with MMS22L."; /evidence="ECO:0000269|PubMed:27338793"; MUTAGEN 571; /note="N->A: Abolished interaction with histone H4 and recruitment to replication forks without affecting interaction with MMS22L."; /evidence="ECO:0000269|PubMed:27338793"; MUTAGEN 604; /note="D->A: Abolished interaction with histone H4 and recruitment to replication forks without affecting interaction with MMS22L."; /evidence="ECO:0000269|PubMed:27338793
uniprot
proteins
protein_family
Tonsoku family
uniprot
proteins
pubmed
11246458
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21055983
uniprot
proteins
pubmed
21055984
uniprot
proteins
pubmed
21055985
uniprot
proteins
pubmed
21113133
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
26527279
uniprot
proteins
pubmed
27338793
uniprot
proteins
pubmed
27797818
uniprot
proteins
pubmed
29478807
uniprot
proteins
pubmed
30773277
uniprot
proteins
pubmed
30773278
uniprot
proteins
pubmed
32959051
uniprot
proteins
pubmed
33857403
uniprot
proteins
pubmed
7738005
uniprot
proteins
pubmed
9242696
uniprot
proteins
sequence_length
1378
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21055983, ECO:0000269|PubMed:21055984, ECO:0000269|PubMed:9242696}. Chromosome {ECO:0000269|PubMed:21055983, ECO:0000269|PubMed:21055984, ECO:0000269|PubMed:26527279, ECO:0000269|PubMed:27338793, ECO:0000269|PubMed:29478807}. Cytoplasm {ECO:0000269|PubMed:7738005}. Note=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). {ECO:0000269|PubMed:21055983, ECO:0000269|PubMed:21055984, ECO:0000269|PubMed:26527279, ECO:0000269|PubMed:27338793, ECO:0000269|PubMed:29478807}.
uniprot
proteins