TONSL_MOUSE
ID TONSL_MOUSE Reviewed; 1363 AA.
AC Q6NZL6; Q8BT74; Q9ER45;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Tonsoku-like protein {ECO:0000303|PubMed:30773278};
DE AltName: Full=Inhibitor of kappa B-related protein;
DE Short=I-kappa-B-related protein;
DE Short=IkappaBR;
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 {ECO:0000303|PubMed:30773278, ECO:0000312|MGI:MGI:1919999};
GN Synonyms=Ikbr, Nfkbil2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 88-487.
RA Norman D.A.M.;
RT "Studies of NF-kappaB and a related protein, IkappaBR, in cardiac
RT myocytes.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1052-1363.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-796, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [7]
RP MUTAGENESIS OF ARG-924.
RX PubMed=30773278; DOI=10.1016/j.ajhg.2019.01.009;
RA Chang H.R., Cho S.Y., Lee J.H., Lee E., Seo J., Lee H.R., Cavalcanti D.P.,
RA Maekitie O., Valta H., Girisha K.M., Lee C., Neethukrishna K.,
RA Bhavani G.S., Shukla A., Nampoothiri S., Phadke S.R., Park M.J.,
RA Ikegawa S., Wang Z., Higgs M.R., Stewart G.S., Jung E., Lee M.S.,
RA Park J.H., Lee E.A., Kim H., Myung K., Jeon W., Lee K., Kim D., Kim O.H.,
RA Choi M., Lee H.W., Kim Y., Cho T.J.;
RT "Hypomorphic mutations in TONSL cause sponastrime dysplasia.";
RL Am. J. Hum. Genet. 104:439-453(2019).
RN [8]
RP INTERACTION WITH HISTONE H3.1.
RX PubMed=35298257; DOI=10.1126/science.abm5320;
RA Davarinejad H., Huang Y.C., Mermaz B., LeBlanc C., Poulet A., Thomson G.,
RA Joly V., Munoz M., Arvanitis-Vigneault A., Valsakumar D., Villarino G.,
RA Ross A., Rotstein B.H., Alarcon E.I., Brunzelle J.S., Voigt P., Dong J.,
RA Couture J.F., Jacob Y.;
RT "The histone H3.1 variant regulates TONSOKU-mediated DNA repair during
RT replication.";
RL Science 375:1281-1286(2022).
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 Specifically binds histone H4 lacking methylation at 'Lys-20'
CC (H4K20me0) and histone H3.1. {ECO:0000250|UniProtKB:Q96HA7}.
CC -!- SUBUNIT: Component of the MMS22L-TONSL complex, a complex at least
CC composed of MMS22L and TONSL/NFKBIL2 (By similarity). Interacts with
CC the MCM complex, the FACT complex and the RPA complex (By similarity).
CC Interacts with MCM5; the interaction is direct (By similarity). Binds
CC histones, with a strong preference for histone H3.1 (histones H3.1 and
CC H3-4/H3.1t) (PubMed:35298257). Interacts (via ANK repeats) with histone
CC H4; specifically binds histone H4 lacking methylation at 'Lys-20'
CC (H4K20me0) (By similarity). May interact with DNAJC9; the interaction
CC seems to be histone-dependent (By similarity).
CC {ECO:0000250|UniProtKB:Q96HA7, ECO:0000269|PubMed:35298257}.
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 ASF1A and the CAF-1 complex: TONSL acts as histone
CC reader that recognizes and binds newly synthesized histones.
CC {ECO:0000250|UniProtKB:Q96HA7}.
CC -!- DOMAIN: The ANK repeats mediate the interaction with the MCM complex
CC and histones, while the LRR repeats mediate the interaction with
CC MMS22L. {ECO:0000250|UniProtKB:Q96HA7}.
CC -!- SIMILARITY: Belongs to the Tonsoku family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH66068.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC25399.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAC08218.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AC156550; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC157566; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC066068; AAH66068.1; ALT_INIT; mRNA.
DR EMBL; AJ294539; CAC08218.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK013272; BAC25399.1; ALT_INIT; mRNA.
DR CCDS; CCDS27580.2; -.
DR RefSeq; NP_898914.3; NM_183091.3.
DR AlphaFoldDB; Q6NZL6; -.
DR SMR; Q6NZL6; -.
DR STRING; 10090.ENSMUSP00000129597; -.
DR iPTMnet; Q6NZL6; -.
DR PhosphoSitePlus; Q6NZL6; -.
DR EPD; Q6NZL6; -.
DR MaxQB; Q6NZL6; -.
DR PaxDb; Q6NZL6; -.
DR PeptideAtlas; Q6NZL6; -.
DR PRIDE; Q6NZL6; -.
DR ProteomicsDB; 259497; -.
DR DNASU; 72749; -.
DR GeneID; 72749; -.
DR KEGG; mmu:72749; -.
DR CTD; 4796; -.
DR MGI; MGI:1919999; Tonsl.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG4308; Eukaryota.
DR InParanoid; Q6NZL6; -.
DR OrthoDB; 56880at2759; -.
DR PhylomeDB; Q6NZL6; -.
DR BioGRID-ORCS; 72749; 39 hits in 109 CRISPR screens.
DR PRO; PR:Q6NZL6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q6NZL6; protein.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005662; C:DNA replication factor A complex; ISO:MGI.
DR GO; GO:0035101; C:FACT complex; ISO:MGI.
DR GO; GO:0042555; C:MCM complex; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0043596; C:nuclear replication fork; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
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; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00028; TPR; 5.
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; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Chromatin regulator; Chromosome; Cytoplasm; DNA damage;
KW DNA repair; Leucine-rich repeat; Methylation; Nucleus; Reference proteome;
KW Repeat; TPR repeat.
FT CHAIN 1..1363
FT /note="Tonsoku-like protein"
FT /id="PRO_0000326635"
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 528..557
FT /note="ANK 1"
FT REPEAT 561..590
FT /note="ANK 2"
FT REPEAT 597..626
FT /note="ANK 3"
FT REPEAT 1060..1081
FT /note="LRR 1"
FT REPEAT 1088..1108
FT /note="LRR 2"
FT REPEAT 1119..1140
FT /note="LRR 3"
FT REPEAT 1147..1168
FT /note="LRR 4"
FT REPEAT 1179..1199
FT /note="LRR 5"
FT REPEAT 1206..1214
FT /note="LRR 6"
FT REPEAT 1238..1261
FT /note="LRR 7"
FT REPEAT 1266..1287
FT /note="LRR 8"
FT REPEAT 1296..1317
FT /note="LRR 9"
FT REPEAT 1322..1343
FT /note="LRR 10"
FT REGION 460..511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 662..786
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 841..866
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 883..909
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..505
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 662..692
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 693..714
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 752..767
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 894..908
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 796
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MUTAGEN 924
FT /note="R->W: Homozygous mice are not viable. Embryos show
FT early lethality along with fetal growth restriction and
FT lack of visible blood vessels in yolk sacs."
FT /evidence="ECO:0000269|PubMed:30773278"
FT CONFLICT 293..294
FT /note="IQ -> NR (in Ref. 3; CAC08218)"
FT /evidence="ECO:0000305"
FT CONFLICT 1106..1107
FT /note="QL -> HV (in Ref. 4; BAC25399)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1363 AA; 151108 MW; 7216519012C69DB2 CRC64;
MTLEQELRQL SKAKTRAQRN GQLREEAAYC HQLGELLASH GRFKDALEEH QQELHLLESV
QDTLGCAVAH RKIGERLAEM ENYSAALKHQ HLYLDLAGSL SNHTELQRAW ATIGRTHLDI
YDHCQSRDSL LQAQAAFEKS LAIVDEKLEG MLTQRELSEM RTRLYLNLGL TCESLQQTAL
CNNYFKKSIF LAEQNHLYED LFRARYNLGA IHWRGGQHSQ AMRCLEGARE CARAMKMRFM
ESECCVLVSQ VLQDLGDFLA AKRALKKAYR LGSQKPNQRV TVCQSLKYVL AVIQLQQQLE
EAEGNDLQGA MAICEQLGDL FSKAGDFPKA AEAYQKQLHL AELLNRPDLE LAVIHVSLAT
TLGDMKDHRK AVHHYEEELR LRKGNALEEA KTWFNIALSR EEAGDAYELL APCFQKAFCC
AQQAQRFQLQ RQILQHLYTV QLKLQPQEAR DTEIRLQELS MAKDTEEEEE EEEEEEEEAS
EAPETSELEL SESEDDADGL SQQLEEDEEL QGCVGRRKVN KWNRRNDMGE TLLHRACIEG
QLRRVQDLVK QGHPLNPRDY CGWTPLHEAC NYGHLEIVRF LLDHGAAVDD PGGQGCDGIT
PLHDALNCGH FEVAELLIER GASVTLRTRK GLSPLETLQQ WVKLYFRDLD LETRQKAATM
EERLQMASSG QASRSSPALQ TIPSNHLFDP ETSPPSSPCP EPSSYTPRPP EASPAPAKVF
LEETVSAVSR PRKTRHRPTS SSSSSEDEDN PSPCRPSQKR LRHTTQQGEV KIPDPPKSRE
TATSSACRAA YQAAIRGVGS AQSRRLVPSL PRGSEEVPAP KTALIPEEEY LAGEWLEVDT
PLTRSGRPST SVSDYERCPA RPRTRVKQSR LTSLDGWCAR TQAGDGSLNA EPAENPSVPR
TSGPNKENYA AGQPLLLVQP PPIRVRVQIQ DNLFLIPVPQ SDIRPVAWLT EQAAQRYFQT
CGLLPRLTLR KDGALLAPQD PIPDVLQSND EVLAEVTSWD LPPLKDRYRR ACLSLGQGEH
QQVLHAMDHQ SSSPSFSACS LALCQAQLTP LLRALKLHTA LRELRLAGNR LGDACATELL
ATLGTTPNLV LLDLSSNHLG QEGLRQLVEG SSGQAALQNL EELDLSMNPL GDGCGQALAS
LLRACPMLST LRLQACGFSS SFFLSHQAAL GGAFQDAVHL KTLSLSYNLL GAPALARVLQ
TLPACTLKRL DLSSVAASKS NSGIIEPVIK YLTKEGCALA HLTLSANCLG DKAVRELSRC
LPCCPSLTSL DLSANPEVSC ASLEELLSAL QERSQGLSFL GLSGCSIQGP LNSDLWDKIF
VQLQELQLCT KDLSTKDRDS VCQRLPEGAC TMDQSSKLFF KCL
