TONSL_DANRE
ID TONSL_DANRE Reviewed; 1427 AA.
AC A9JR78; Q569P2;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Tonsoku-like protein {ECO:0000305};
DE AltName: Full=NF-kappa-B inhibitor-like protein 2;
DE AltName: Full=Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2;
GN Name=tonsl; Synonyms=nfkbil2; ORFNames=im:7145273, zgc:171416;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB; TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=30773277; DOI=10.1016/j.ajhg.2019.01.007;
RG University of Washington Center for Mendelian Genomics;
RG Undiagnosed Diseases Network;
RA Burrage L.C., Reynolds J.J., Baratang N.V., Phillips J.B., Wegner J.,
RA McFarquhar A., Higgs M.R., Christiansen A.E., Lanza D.G., Seavitt J.R.,
RA Jain M., Li X., Parry D.A., Raman V., Chitayat D., Chinn I.K.,
RA Bertuch A.A., Karaviti L., Schlesinger A.E., Earl D., Bamshad M.,
RA Savarirayan R., Doddapaneni H., Muzny D., Jhangiani S.N., Eng C.M.,
RA Gibbs R.A., Bi W., Emrick L., Rosenfeld J.A., Postlethwait J.,
RA Westerfield M., Dickinson M.E., Beaudet A.L., Ranza E., Huber C.,
RA Cormier-Daire V., Shen W., Mao R., Heaney J.D., Orange J.S., Bertola D.,
RA Yamamoto G.L., Baratela W.A.R., Butler M.G., Ali A., Adeli M., Cohn D.H.,
RA Krakow D., Jackson A.P., Lees M., Offiah A.C., Carlston C.M., Carey J.C.,
RA Stewart G.S., Bacino C.A., Campeau P.M., Lee B.;
RT "Bi-allelic variants in TONSL cause sponastrime dysplasia and a spectrum of
RT skeletal dysplasia phenotypes.";
RL Am. J. Hum. Genet. 104:422-438(2019).
CC -!- FUNCTION: Component of the MMS22L-TONSL complex, a complex that
CC promotes homologous recombination-mediated repair of double-strand
CC breaks (DSBs) at stalled or collapsed replication forks. The MMS22L-
CC TONSL complex is required to maintain genome integrity during DNA
CC replication. It mediates the assembly of RAD51 filaments on single-
CC stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs
CC following histone replacement by histone chaperones and eviction of the
CC replication protein A complex (RPA/RP-A) from DSBs. Following
CC recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of
CC RAD51 filaments and subsequent homologous recombination. Within the
CC complex, TONSL acts as histone reader, which recognizes and binds newly
CC synthesized histones following their replacement by histone chaperones.
CC {ECO:0000250|UniProtKB:Q96HA7}.
CC -!- SUBUNIT: Component of the MMS22L-TONSL complex. Binds histones, with a
CC strong preference for histone H3.1 (histones H3.1 and H3-4/H3.1t).
CC {ECO:0000250|UniProtKB:Q96HA7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96HA7}.
CC Chromosome {ECO:0000250|UniProtKB:Q96HA7}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q96HA7}. Note=Mainly nuclear. Localizes to DNA
CC damage sites, accumulates at stressed replication forks. Recruited to
CC stalled or collapsed replication forks following histone replacement by
CC histone chaperones: TONSL acts as histone reader that recognizes and
CC binds newly synthesized histones. {ECO:0000250|UniProtKB:Q96HA7}.
CC -!- DISRUPTION PHENOTYPE: Tonsl deficiency causes growth deficits,
CC vertebral abnormalities, reduced neutrophil numbers, and death at early
CC stages of larvae development. {ECO:0000269|PubMed:30773277}.
CC -!- SIMILARITY: Belongs to the Tonsoku family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH92364.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC092364; AAH92364.1; ALT_INIT; mRNA.
DR EMBL; BC155547; AAI55548.1; -; mRNA.
DR RefSeq; NP_001104618.1; NM_001111148.1.
DR AlphaFoldDB; A9JR78; -.
DR SMR; A9JR78; -.
DR STRING; 7955.ENSDARP00000096098; -.
DR PaxDb; A9JR78; -.
DR PeptideAtlas; A9JR78; -.
DR GeneID; 492655; -.
DR KEGG; dre:492655; -.
DR CTD; 4796; -.
DR ZFIN; ZDB-GENE-041111-230; tonsl.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG4308; Eukaryota.
DR InParanoid; A9JR78; -.
DR OrthoDB; 56880at2759; -.
DR PhylomeDB; A9JR78; -.
DR PRO; PR:A9JR78; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043596; C:nuclear replication fork; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0140566; F:histone reader activity; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR Gene3D; 1.25.40.10; -; 2.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF13516; LRR_6; 2.
DR Pfam; PF13176; TPR_7; 2.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00367; LRR_CC; 3.
DR SMART; SM00028; TPR; 8.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF48452; SSF48452; 3.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
DR PROSITE; PS50005; TPR; 7.
DR PROSITE; PS50293; TPR_REGION; 3.
PE 2: Evidence at transcript level;
KW ANK repeat; Chromatin regulator; Chromosome; Cytoplasm; DNA damage;
KW DNA repair; Leucine-rich repeat; Nucleus; Reference proteome; Repeat;
KW TPR repeat.
FT CHAIN 1..1427
FT /note="Tonsoku-like protein"
FT /id="PRO_0000326636"
FT REPEAT 27..60
FT /note="TPR 1"
FT REPEAT 67..100
FT /note="TPR 2"
FT REPEAT 107..147
FT /note="TPR 3"
FT REPEAT 162..195
FT /note="TPR 4"
FT REPEAT 202..235
FT /note="TPR 5"
FT REPEAT 242..275
FT /note="TPR 6"
FT REPEAT 311..344
FT /note="TPR 7"
FT REPEAT 352..385
FT /note="TPR 8"
FT REPEAT 522..551
FT /note="ANK 1"
FT REPEAT 555..584
FT /note="ANK 2"
FT REPEAT 591..620
FT /note="ANK 3"
FT REPEAT 1113..1137
FT /note="LRR 1"
FT REPEAT 1141..1168
FT /note="LRR 2"
FT REPEAT 1174..1197
FT /note="LRR 3"
FT REPEAT 1234..1258
FT /note="LRR 4"
FT REPEAT 1293..1316
FT /note="LRR 5"
FT REPEAT 1321..1346
FT /note="LRR 6"
FT REPEAT 1377..1400
FT /note="LRR 7"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 465..502
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 692..801
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 865..922
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 941..961
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 467..501
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..801
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 877..919
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 1068
FT /note="E -> Q (in Ref. 1; AAH92364)"
FT /evidence="ECO:0000305"
FT CONFLICT 1305
FT /note="G -> E (in Ref. 1; AAH92364)"
FT /evidence="ECO:0000305"
FT CONFLICT 1348
FT /note="V -> M (in Ref. 1; AAH92364)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1427 AA; 158305 MW; BD3B7E54903CCA11 CRC64;
MTSTKEIKQL QKAKSKAQSS NNLKEEASLC NQLGEVYAKT GDYQAAIEEH RQELALSEIL
HDVIGSAVAN RKIGECYAEL GNIEAALKHQ RLHLNLARSV HDAAEEQRAL ATIGRTYLFL
FDSDQSANSL KHAEDAFKRS LAIVDERLEG TVSPREISEM KARLLLNLGC VYDGMKEPQR
CSDLIRQSIY IAEKNNLLED LYRANFNLGS IHFRNGQHSR AMRCFEQSKE CARKMKDKFS
ESECFHSIGK ILLHLGDFSA ARRSLKKAFC LGSQQPSDRE AVKKDFRHAI RGCQLEQTAA
EVTQKFSHEA LDLSEQLGDL YCKVGCYSKA LEAYQTQLAC AEALAKPARE LAVIHVSLAA
TYTDLRQHHR AVEHYRQELQ LRKGNPKEEC ETWLNMAVCQ EEMCQSMETL DHCFTSALNC
AEKSGLNKLQ RRVLRVWLQA QRRCGSSQCD DTEARLMELC ERDGLSLDQS EDEDEEDEVD
NSEPLEDSDI QYSESDDEDL EGYDKMVTGR RKTQRWNRRN EKGETVLHRA CIEGNLKQVQ
YLIEQGHPVN VRDYCGWTPL HESCNYGHQE IVAFLLDRGA NVNDPGGREC GGITPLHDTL
SCGHFSVARL LVLRGASVTV RNSKGHTPLD TLRQWFKTYS GQLDPETKQE CLETEKLIKR
ALSGDVSVVC AAPRQQKELQ DSQLFDAEYS EPLLRESPPS PPPITRPAAT VPTSKDSAPK
HRSTSASTRR PRGMEVDVLY GDDSSSSDNP DSDCSLSPLR PVRSRPRSPP AQSPQEVPSS
QELPSVYGIK ETTVPPQSES GRLEYQKAMQ NLGSAKSRLF SQSLSDPAFT STPAVSANSR
AALVPEDQYL ADDWLEDDLI DMQPKKKRRV SEHNATRETT SRSQNNSSTI AEVPPRVQSC
SSRGSLSLKK GSNKPRQVKM NQLPGMVMLG RREVSRSQSP IMTQESDHIQ EPAPPSHQAM
PPASFQNRAA HVPAPIRMRV KVQDNVFLIP VPHSEADSCT VAWLCDQAAQ RYYQMCGLLP
RLSLQKEGAL LLPTDPLLAV LHTNEEVLAE VCSWDLPPLP ERYRKACESL GVEENRRVSR
VCEVQDSSSC VSVCGLSLSP ASLNPLLRAL KLQASLTELR ISANRLNDEL LPEMMAAAAT
MPRLRVLDIS ANQITGEGLR KASDAFETRS QAAFPCLEEL NLSMNPLGDG WTQALASLLS
SCPLLSSLSL QACGLSARFL QQHRLLLANA MASTGNMRSV CLSHNALGST GFELVLKTLP
MHCLTHLELS AVCRGPSDQP SMEILTKLLA QGDCPLTHLN LSGNGLTDHS VLLLARCLPV
CPSLVSLDLS ANPLVTSTGL HSLLNGLVEA RRPLGHLNLQ GCQVSGPLAE DCLDSLSDHI
RDLRLCSQSL NKLDQDALQQ SWKRRTEAVH IFSRNSKCML SISSPSH
