NHEJ1_HUMAN
ID NHEJ1_HUMAN Reviewed; 299 AA.
AC Q9H9Q4; B8ZZA4; Q4ZFW7; Q6IA64; Q96JS9;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Non-homologous end-joining factor 1 {ECO:0000305};
DE AltName: Full=Protein cernunnos {ECO:0000303|PubMed:16439204};
DE AltName: Full=XRCC4-like factor {ECO:0000303|PubMed:16439205};
GN Name=NHEJ1 {ECO:0000303|PubMed:17191205, ECO:0000312|HGNC:HGNC:25737};
GN Synonyms=XLF {ECO:0000303|PubMed:16439205};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND VARIANTS NHEJ1-SCID GLY-57 AND ARG-123.
RC TISSUE=Thymus;
RX PubMed=16439204; DOI=10.1016/j.cell.2005.12.030;
RA Buck D., Malivert L., de Chasseval R., Barraud A., Fondaneche M.-C.,
RA Sanal O., Plebani A., Stephan J.-L., Hufnagel M., le Deist F., Fischer A.,
RA Durandy A., de Villartay J.-P., Revy P.;
RT "Cernunnos, a novel nonhomologous end-joining factor, is mutated in human
RT immunodeficiency with microcephaly.";
RL Cell 124:287-299(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 177-299 (ISOFORM 2).
RC TISSUE=Bone marrow, and Skin;
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 [6]
RP DISEASE.
RX PubMed=12604777; DOI=10.1073/pnas.0437964100;
RA Dai Y., Kysela B., Hanakahi L.A., Manolis K., Riballo E., Stumm M.,
RA Harville T.O., West S.C., Oettinger M.A., Jeggo P.A.;
RT "Nonhomologous end joining and V(D)J recombination require an additional
RT factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2462-2467(2003).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH XRCC4, AND INVOLVEMENT IN
RP NHEJ1-SCID.
RX PubMed=16439205; DOI=10.1016/j.cell.2005.12.031;
RA Ahnesorg P., Smith P., Jackson S.P.;
RT "XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA
RT nonhomologous end-joining.";
RL Cell 124:301-313(2006).
RN [8]
RP INTERACTION WITH XRCC4-LIG4 COMPLEX.
RX PubMed=16571728; DOI=10.1074/jbc.c500473200;
RA Callebaut I., Malivert L., Fischer A., Mornon J.P., Revy P.,
RA de Villartay J.P.;
RT "Cernunnos interacts with the XRCC4 x DNA-ligase IV complex and is
RT homologous to the yeast nonhomologous end-joining factor Nej1.";
RL J. Biol. Chem. 281:13857-13860(2006).
RN [9]
RP CHROMOSOMAL TRANSLOCATION.
RX PubMed=17191205; DOI=10.1002/humu.20450;
RA Cantagrel V., Lossi A.M., Lisgo S., Missirian C., Borges A., Philip N.,
RA Fernandez C., Cardoso C., Figarella-Branger D., Moncla A., Lindsay S.,
RA Dobyns W.B., Villard L.;
RT "Truncation of NHEJ1 in a patient with polymicrogyria.";
RL Hum. Mutat. 28:356-364(2007).
RN [10]
RP FUNCTION.
RX PubMed=17717001; DOI=10.1093/nar/gkm579;
RA Gu J., Lu H., Tsai A.G., Schwarz K., Lieber M.R.;
RT "Single-stranded DNA ligation and XLF-stimulated incompatible DNA end
RT ligation by the XRCC4-DNA ligase IV complex: influence of terminal DNA
RT sequence.";
RL Nucleic Acids Res. 35:5755-5762(2007).
RN [11]
RP INTERACTION WITH XRCC4-LIG4 COMPLEX, DNA-BINDING, AND CHARACTERIZATION OF
RP VARIANT NHEJ1-SCID GLY-57.
RX PubMed=17317666; DOI=10.1074/jbc.m609904200;
RA Lu H., Pannicke U., Schwarz K., Lieber M.R.;
RT "Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA
RT ligase IV activity.";
RL J. Biol. Chem. 282:11155-11162(2007).
RN [12]
RP FUNCTION.
RX PubMed=17470781; DOI=10.1073/pnas.0702620104;
RA Tsai C.J., Kim S.A., Chu G.;
RT "Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA
RT ends.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7851-7856(2007).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-132; SER-203;
RP SER-245; SER-251; SER-263 AND THR-266, AND MUTAGENESIS OF SER-132; SER-203;
RP SER-245; SER-251; SER-263 AND THR-266.
RX PubMed=18644470; DOI=10.1016/j.dnarep.2008.06.015;
RA Yu Y., Mahaney B.L., Yano K., Ye R., Fang S., Douglas P., Chen D.J.,
RA Lees-Miller S.P.;
RT "DNA-PK and ATM phosphorylation sites in XLF/Cernunnos are not required for
RT repair of DNA double strand breaks.";
RL DNA Repair 7:1680-1692(2008).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=18064046; DOI=10.1038/sj.embor.7401137;
RA Yano K., Morotomi-Yano K., Wang S.Y., Uematsu N., Lee K.J., Asaithamby A.,
RA Weterings E., Chen D.J.;
RT "Ku recruits XLF to DNA double-strand breaks.";
RL EMBO Rep. 9:91-96(2008).
RN [15]
RP FUNCTION.
RX PubMed=19056826; DOI=10.1093/nar/gkn957;
RA Riballo E., Woodbine L., Stiff T., Walker S.A., Goodarzi A.A., Jeggo P.A.;
RT "XLF-Cernunnos promotes DNA ligase IV-XRCC4 re-adenylation following
RT ligation.";
RL Nucleic Acids Res. 37:482-492(2009).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH XRCC4, AND MUTAGENESIS OF
RP GLN-11; TRP-13; TRP-15; LEU-24; LYS-26; LEU-37; ASP-40; LEU-41; GLN-43;
RP ARG-57; LEU-61; ARG-64; LEU-65; LEU-115; PRO-116; PHE-117; TYR-118;
RP TRP-119; CYS-123; LEU-135; ARG-137; PRO-138; LEU-139; ARG-178; GLU-182 AND
RP 189-PHE-LEU-190.
RX PubMed=20558749; DOI=10.1074/jbc.m110.138156;
RA Malivert L., Ropars V., Nunez M., Drevet P., Miron S., Faure G.,
RA Guerois R., Mornon J.P., Revy P., Charbonnier J.B., Callebaut I.,
RA de Villartay J.P.;
RT "Delineation of the Xrcc4-interacting region in the globular head domain of
RT cernunnos/XLF.";
RL J. Biol. Chem. 285:26475-26483(2010).
RN [17]
RP FUNCTION, INTERACTION WITH XRCC4, PHOSPHORYLATION AT SER-132; SER-203;
RP SER-245; SER-251; SER-263 AND THR-266, AND MUTAGENESIS OF SER-132; SER-203;
RP SER-245; SER-251; SER-263 AND THR-266.
RX PubMed=22228831; DOI=10.1093/nar/gkr1315;
RA Roy S., Andres S.N., Vergnes A., Neal J.A., Xu Y., Yu Y., Lees-Miller S.P.,
RA Junop M., Modesti M., Meek K.;
RT "XRCC4's interaction with XLF is required for coding (but not signal) end
RT joining.";
RL Nucleic Acids Res. 40:1684-1694(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP SUBUNIT.
RX PubMed=25941166; DOI=10.1038/cdd.2015.22;
RA Craxton A., Somers J., Munnur D., Jukes-Jones R., Cain K., Malewicz M.;
RT "XLS (c9orf142) is a new component of mammalian DNA double-stranded break
RT repair.";
RL Cell Death Differ. 22:890-897(2015).
RN [20]
RP FUNCTION, INTERACTION WITH XRCC4, AND MUTAGENESIS OF LEU-115.
RX PubMed=26100018; DOI=10.1128/mcb.01503-14;
RA Roy S., de Melo A.J., Xu Y., Tadi S.K., Negrel A., Hendrickson E.,
RA Modesti M., Meek K.;
RT "XRCC4/XLF interaction is variably required for DNA repair and is not
RT required for ligase IV stimulation.";
RL Mol. Cell. Biol. 35:3017-3028(2015).
RN [21]
RP SUBUNIT.
RX PubMed=25670504; DOI=10.1038/ncomms7233;
RA Xing M., Yang M., Huo W., Feng F., Wei L., Jiang W., Ning S., Yan Z.,
RA Li W., Wang Q., Hou M., Dong C., Guo R., Gao G., Ji J., Zha S., Lan L.,
RA Liang H., Xu D.;
RT "Interactome analysis identifies a new paralogue of XRCC4 in non-homologous
RT end joining DNA repair pathway.";
RL Nat. Commun. 6:6233-6233(2015).
RN [22]
RP SUBUNIT.
RX PubMed=25574025; DOI=10.1126/science.1261971;
RA Ochi T., Blackford A.N., Coates J., Jhujh S., Mehmood S., Tamura N.,
RA Travers J., Wu Q., Draviam V.M., Robinson C.V., Blundell T.L.,
RA Jackson S.P.;
RT "DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote
RT DNA double-strand break repair.";
RL Science 347:185-188(2015).
RN [23]
RP FUNCTION, INTERACTION WITH XRCC4, AND SUBCELLULAR LOCATION.
RX PubMed=27437582; DOI=10.1038/nature18643;
RA Brouwer I., Sitters G., Candelli A., Heerema S.J., Heller I., de Melo A.J.,
RA Zhang H., Normanno D., Modesti M., Peterman E.J., Wuite G.J.;
RT "Sliding sleeves of XRCC4-XLF bridge DNA and connect fragments of broken
RT DNA.";
RL Nature 535:566-569(2016).
RN [24]
RP XLM MOTIF.
RX PubMed=27063109; DOI=10.1038/ncomms11242;
RA Grundy G.J., Rulten S.L., Arribas-Bosacoma R., Davidson K., Kozik Z.,
RA Oliver A.W., Pearl L.H., Caldecott K.W.;
RT "The Ku-binding motif is a conserved module for recruitment and stimulation
RT of non-homologous end-joining proteins.";
RL Nat. Commun. 7:11242-11242(2016).
RN [25]
RP FUNCTION, PHOSPHORYLATION AT SER-132; SER-203; SER-245 AND SER-251, AND
RP MUTAGENESIS OF SER-132; SER-203; SER-245 AND SER-251.
RX PubMed=28500754; DOI=10.7554/elife.22900;
RA Normanno D., Negrel A., de Melo A.J., Betzi S., Meek K., Modesti M.;
RT "Mutational phospho-mimicry reveals a regulatory role for the XRCC4 and XLF
RT C-terminal tails in modulating DNA bridging during classical non-homologous
RT end joining.";
RL Elife 6:0-0(2017).
RN [26]
RP FUNCTION, AND INTERACTION WITH POLL.
RX PubMed=30250067; DOI=10.1038/s41467-018-06127-y;
RA Craxton A., Munnur D., Jukes-Jones R., Skalka G., Langlais C., Cain K.,
RA Malewicz M.;
RT "PAXX and its paralogs synergistically direct DNA polymerase lambda
RT activity in DNA repair.";
RL Nat. Commun. 9:3877-3877(2018).
RN [27] {ECO:0007744|PDB:2R9A}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1-224, FUNCTION, INTERACTION WITH
RP XRCC4, SUBUNIT, AND MUTAGENESIS OF ILE-105; GLU-111; LEU-115; GLU-169;
RP LEU-174; ARG-178; LEU-179; GLU-185; ILE-195 AND SER-278.
RX PubMed=18158905; DOI=10.1016/j.molcel.2007.10.024;
RA Andres S.N., Modesti M., Tsai C.J., Chu G., Junop M.S.;
RT "Crystal structure of human XLF: a twist in nonhomologous DNA end-
RT joining.";
RL Mol. Cell 28:1093-1101(2007).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-233, COILED-COIL REGION, AND
RP SUBUNIT.
RX PubMed=18046455; DOI=10.1038/sj.emboj.7601942;
RA Li Y., Chirgadze D.Y., Bolanos-Garcia V.M., Sibanda B.L., Davies O.R.,
RA Ahnesorg P., Jackson S.P., Blundell T.L.;
RT "Crystal structure of human XLF/Cernunnos reveals unexpected differences
RT from XRCC4 with implications for NHEJ.";
RL EMBO J. 27:290-300(2008).
RN [29]
RP CRYSTALLIZATION.
RX PubMed=22102241; DOI=10.1107/s1744309111033549;
RA Andres S.N., Junop M.S.;
RT "Crystallization and preliminary X-ray diffraction analysis of the human
RT XRCC4-XLF complex.";
RL Acta Crystallogr. F 67:1399-1402(2011).
RN [30] {ECO:0007744|PDB:3W03}
RP X-RAY CRYSTALLOGRAPHY (8.49 ANGSTROMS) OF 1-233 IN COMPLEX WITH NHEJ1, AND
RP INTERACTION WITH NHEJ1.
RX PubMed=21936820; DOI=10.1042/bst0391387;
RA Wu Q., Ochi T., Matak-Vinkovic D., Robinson C.V., Chirgadze D.Y.,
RA Blundell T.L.;
RT "Non-homologous end-joining partners in a helical dance: structural studies
RT of XLF-XRCC4 interactions.";
RL Biochem. Soc. Trans. 39:1387-1392(2011).
RN [31] {ECO:0007744|PDB:3SR2}
RP X-RAY CRYSTALLOGRAPHY (3.97 ANGSTROMS) OF 1-224 IN COMPLEX WITH XRCC4,
RP FUNCTION, DOMAIN, INTERACTION WITH XRCC4, AND MUTAGENESIS OF 64-ARG-LEU-65
RP AND LEU-115.
RX PubMed=21775435; DOI=10.1074/jbc.m111.272641;
RA Hammel M., Rey M., Yu Y., Mani R.S., Classen S., Liu M., Pique M.E.,
RA Fang S., Mahaney B.L., Weinfeld M., Schriemer D.C., Lees-Miller S.P.,
RA Tainer J.A.;
RT "XRCC4 protein interactions with XRCC4-like factor (XLF) create an extended
RT grooved scaffold for DNA ligation and double strand break repair.";
RL J. Biol. Chem. 286:32638-32650(2011).
RN [32] {ECO:0007744|PDB:3RWR}
RP X-RAY CRYSTALLOGRAPHY (3.94 ANGSTROMS) OF 1-224 IN COMPLEX WITH XRCC4,
RP FUNCTION, INTERACTION WITH XRCC4, AND MUTAGENESIS OF LEU-115 AND LYS-293.
RX PubMed=22287571; DOI=10.1093/nar/gks022;
RA Andres S.N., Vergnes A., Ristic D., Wyman C., Modesti M., Junop M.;
RT "A human XRCC4-XLF complex bridges DNA.";
RL Nucleic Acids Res. 40:1868-1878(2012).
RN [33] {ECO:0007744|PDB:3Q4F}
RP X-RAY CRYSTALLOGRAPHY (5.50 ANGSTROMS) OF 1-224 IN COMPLEX WITH XRCC4,
RP FUNCTION, INTERACTION WITH XRCC4, AND MUTAGENESIS OF ARG-64 AND GLU-111.
RX PubMed=21768349; DOI=10.1073/pnas.1100758108;
RA Ropars V., Drevet P., Legrand P., Baconnais S., Amram J., Faure G.,
RA Marquez J.A., Pietrement O., Guerois R., Callebaut I., Le Cam E., Revy P.,
RA de Villartay J.P., Charbonnier J.B.;
RT "Structural characterization of filaments formed by human Xrcc4-
RT Cernunnos/XLF complex involved in nonhomologous DNA end-joining.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:12663-12668(2011).
RN [34] {ECO:0007744|PDB:7LSY, ECO:0007744|PDB:7LT3}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.6 ANGSTROMS) IN COMPLEX WITH THE NHEJ
RP COMPLEX, AND IDENTIFICATION IN THE NHEJ COMPLEX.
RX PubMed=33854234; DOI=10.1038/s41586-021-03458-7;
RA Chen S., Lee L., Naila T., Fishbain S., Wang A., Tomkinson A.E.,
RA Lees-Miller S.P., He Y.;
RT "Structural basis of long-range to short-range synaptic transition in
RT NHEJ.";
RL Nature 593:294-298(2021).
CC -!- FUNCTION: DNA repair protein involved in DNA non-homologous end joining
CC (NHEJ); required for double-strand break (DSB) repair and V(D)J
CC recombination (PubMed:16439204, PubMed:16439205, PubMed:17717001,
CC PubMed:17317666, PubMed:17470781, PubMed:18644470, PubMed:20558749,
CC PubMed:26100018, PubMed:18158905). Plays a key role in NHEJ by
CC promoting the ligation of various mismatched and non-cohesive ends
CC (PubMed:17717001, PubMed:17470781, PubMed:19056826). Together with
CC PAXX, collaborates with DNA polymerase lambda (POLL) to promote joining
CC of non-cohesive DNA ends (PubMed:30250067, PubMed:25670504). May act in
CC concert with XRCC5-XRCC6 (Ku) to stimulate XRCC4-mediated joining of
CC blunt ends and several types of mismatched ends that are non-
CC complementary or partially complementary (PubMed:16439204,
CC PubMed:16439205, PubMed:17317666, PubMed:17470781). Associates with
CC XRCC4 to form alternating helical filaments that bridge DNA and act
CC like a bandage, holding together the broken DNA until it is repaired
CC (PubMed:22228831, PubMed:26100018, PubMed:28500754, PubMed:27437582,
CC PubMed:21775435, PubMed:22287571, PubMed:21768349). The XRCC4-NHEJ1/XLF
CC subcomplex binds to the DNA fragments of a DSB in a highly diffusive
CC manner and robustly bridges two independent DNA molecules, holding the
CC broken DNA fragments in close proximity to one other (PubMed:28500754,
CC PubMed:27437582). The mobility of the bridges ensures that the ends
CC remain accessible for further processing by other repair factors
CC (PubMed:27437582). Binds DNA in a length-dependent manner
CC (PubMed:17317666, PubMed:18158905). {ECO:0000269|PubMed:16439204,
CC ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:17317666,
CC ECO:0000269|PubMed:17470781, ECO:0000269|PubMed:17717001,
CC ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:18644470,
CC ECO:0000269|PubMed:19056826, ECO:0000269|PubMed:20558749,
CC ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435,
CC ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571,
CC ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:26100018,
CC ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28500754,
CC ECO:0000269|PubMed:30250067}.
CC -!- SUBUNIT: Homodimer; mainly exists as a homodimer when not associated
CC with XRCC4 (PubMed:18046455, PubMed:25574025, PubMed:25670504,
CC PubMed:25941166, PubMed:18158905). Interacts with XRCC4; the
CC interaction is direct and is mediated via a head-to-head interaction
CC between N-terminal head regions (PubMed:16439205, PubMed:20558749,
CC PubMed:22228831, PubMed:26100018, PubMed:18158905, PubMed:21936820,
CC PubMed:21775435, PubMed:22287571, PubMed:21768349, PubMed:27437582).
CC Component of the core long-range non-homologous end joining (NHEJ)
CC complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4,
CC XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:16571728, PubMed:17317666,
CC PubMed:33854234). Additional component of the NHEJ complex includes
CC PAXX (PubMed:25574025, PubMed:25941166). Following autophosphorylation,
CC PRKDC dissociates from DNA, leading to formation of the short-range
CC NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and
CC NHEJ1/XLF (PubMed:33854234). Interacts with POLL (DNA polymerase
CC lambda); promoting POLL recruitment to double-strand breaks (DSBs) and
CC stimulation of the end-filling activity of POLL (PubMed:30250067).
CC {ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:16571728,
CC ECO:0000269|PubMed:17317666, ECO:0000269|PubMed:18046455,
CC ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:20558749,
CC ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435,
CC ECO:0000269|PubMed:21936820, ECO:0000269|PubMed:22228831,
CC ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25574025,
CC ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:25941166,
CC ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:27437582,
CC ECO:0000269|PubMed:30250067, ECO:0000269|PubMed:33854234}.
CC -!- INTERACTION:
CC Q9H9Q4; P49917: LIG4; NbExp=5; IntAct=EBI-847807, EBI-847896;
CC Q9H9Q4; Q13426: XRCC4; NbExp=11; IntAct=EBI-847807, EBI-717592;
CC Q9H9Q4-1; Q13426: XRCC4; NbExp=4; IntAct=EBI-15891382, EBI-717592;
CC Q9H9Q4-1; Q13426-2: XRCC4; NbExp=3; IntAct=EBI-15891382, EBI-15891375;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16439204,
CC ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:20558749}. Chromosome
CC {ECO:0000269|PubMed:18064046, ECO:0000269|PubMed:18644470,
CC ECO:0000269|PubMed:27437582}. Note=Localizes to site of double-strand
CC breaks; recruitment is dependent on XRCC5-XRCC6 (Ku) heterodimer.
CC {ECO:0000269|PubMed:18064046, ECO:0000269|PubMed:18644470,
CC ECO:0000269|PubMed:27437582}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H9Q4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H9Q4-2; Sequence=VSP_017689;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:16439204}.
CC -!- DOMAIN: The coiled-coil region mediates homodimerization.
CC {ECO:0000269|PubMed:18046455}.
CC -!- DOMAIN: The Leu-lock (Leu-115) site inserts into a hydrophobic pocket
CC in XRCC4. {ECO:0000269|PubMed:21775435}.
CC -!- PTM: Phosphorylated by PRKDC at the C-terminus in response to DNA
CC damage (PubMed:18644470, PubMed:22228831, PubMed:28500754).
CC Phosphorylations by PRKDC at the C-terminus of XRCC4 and NHEJ1/XLF are
CC highly redundant and regulate ability of the XRCC4-NHEJ1/XLF subcomplex
CC to bridge DNA (PubMed:22228831, PubMed:28500754). Phosphorylation does
CC not prevent interaction with XRCC4 but disrupts ability to bridge DNA
CC and promotes detachment from DNA (PubMed:22228831, PubMed:28500754).
CC {ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:22228831,
CC ECO:0000269|PubMed:28500754}.
CC -!- DISEASE: Severe combined immunodeficiency due to NHEJ1 deficiency
CC (NHEJ1-SCID) [MIM:611291]: SCID refers to a genetically and clinically
CC heterogeneous group of rare congenital disorders characterized by
CC impairment of both humoral and cell-mediated immunity, leukopenia and
CC low or absent antibody levels. Patients with SCID present in infancy
CC with recurrent, persistent infections by opportunistic organisms. The
CC common characteristic of all types of SCID is absence of T-cell-
CC mediated cellular immunity due to a defect in T-cell development.
CC NHEJ1-SCID is characterized by a profound T- and B-lymphocytopenia
CC associated with increased cellular sensitivity to ionizing radiation,
CC microcephaly and growth retardation. Some patients may manifest SCID
CC with sensitivity to ionizing radiation without microcephaly and mild
CC growth retardation, probably due to hypomorphic NHEJ1 mutations.
CC {ECO:0000269|PubMed:16439204, ECO:0000269|PubMed:16439205,
CC ECO:0000269|PubMed:17317666}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=A chromosomal aberration involving NHEJ1 is found in a
CC patient with polymicrogyria. Translocation t(2;7)(q35;p22).
CC {ECO:0000269|PubMed:12604777}.
CC -!- MISCELLANEOUS: Was named 'Cernunnos' after the enigmatic Celtic god of
CC hunting, the underworld and fertility.
CC -!- SIMILARITY: Belongs to the XRCC4-XLF family. XLF subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NHEJ1base; Note=NHEJ1 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/NHEJ1base/";
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DR EMBL; AJ972687; CAI99410.1; -; mRNA.
DR EMBL; AK022672; BAB14168.1; -; mRNA.
DR EMBL; CR457291; CAG33572.1; -; mRNA.
DR EMBL; AC020575; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068946; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097468; AAX88921.1; -; Genomic_DNA.
DR EMBL; BC008210; AAH08210.2; -; mRNA.
DR EMBL; BC012732; AAH12732.1; -; mRNA.
DR EMBL; BC030986; AAH30986.1; -; mRNA.
DR CCDS; CCDS2432.1; -. [Q9H9Q4-1]
DR RefSeq; NP_079058.1; NM_024782.2. [Q9H9Q4-1]
DR PDB; 2QM4; X-ray; 2.30 A; A/B/C/D=1-233.
DR PDB; 2R9A; X-ray; 2.50 A; A/B=1-224.
DR PDB; 3Q4F; X-ray; 5.50 A; A/B/E/F=1-224.
DR PDB; 3RWR; X-ray; 3.94 A; D/E/H/I/L/M/O/Q/S/T/W/X=1-224.
DR PDB; 3SR2; X-ray; 3.97 A; C/D/G/H=1-224.
DR PDB; 3W03; X-ray; 8.49 A; A/B=1-233.
DR PDB; 6ERG; X-ray; 2.90 A; C/F=287-299.
DR PDB; 6ERH; X-ray; 2.80 A; M/T=281-299.
DR PDB; 7LSY; EM; 8.40 A; H/I=1-299.
DR PDB; 7LT3; EM; 4.60 A; H/I=1-299.
DR PDB; 7NFC; EM; 4.14 A; Q/R=1-299.
DR PDB; 7NFE; EM; 4.29 A; F/G=1-299.
DR PDBsum; 2QM4; -.
DR PDBsum; 2R9A; -.
DR PDBsum; 3Q4F; -.
DR PDBsum; 3RWR; -.
DR PDBsum; 3SR2; -.
DR PDBsum; 3W03; -.
DR PDBsum; 6ERG; -.
DR PDBsum; 6ERH; -.
DR PDBsum; 7LSY; -.
DR PDBsum; 7LT3; -.
DR PDBsum; 7NFC; -.
DR PDBsum; 7NFE; -.
DR AlphaFoldDB; Q9H9Q4; -.
DR SMR; Q9H9Q4; -.
DR BioGRID; 122931; 15.
DR CORUM; Q9H9Q4; -.
DR DIP; DIP-37959N; -.
DR IntAct; Q9H9Q4; 10.
DR MINT; Q9H9Q4; -.
DR STRING; 9606.ENSP00000349313; -.
DR GlyGen; Q9H9Q4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H9Q4; -.
DR PhosphoSitePlus; Q9H9Q4; -.
DR BioMuta; NHEJ1; -.
DR DMDM; 74734059; -.
DR EPD; Q9H9Q4; -.
DR jPOST; Q9H9Q4; -.
DR MassIVE; Q9H9Q4; -.
DR MaxQB; Q9H9Q4; -.
DR PaxDb; Q9H9Q4; -.
DR PeptideAtlas; Q9H9Q4; -.
DR PRIDE; Q9H9Q4; -.
DR ProteomicsDB; 81350; -. [Q9H9Q4-1]
DR ProteomicsDB; 81351; -. [Q9H9Q4-2]
DR Antibodypedia; 34300; 474 antibodies from 32 providers.
DR DNASU; 79840; -.
DR Ensembl; ENST00000356853.10; ENSP00000349313.5; ENSG00000187736.13. [Q9H9Q4-1]
DR Ensembl; ENST00000409720.5; ENSP00000387290.1; ENSG00000187736.13. [Q9H9Q4-2]
DR GeneID; 79840; -.
DR KEGG; hsa:79840; -.
DR MANE-Select; ENST00000356853.10; ENSP00000349313.5; NM_024782.3; NP_079058.1.
DR UCSC; uc002vjp.5; human. [Q9H9Q4-1]
DR CTD; 79840; -.
DR DisGeNET; 79840; -.
DR GeneCards; NHEJ1; -.
DR HGNC; HGNC:25737; NHEJ1.
DR HPA; ENSG00000187736; Low tissue specificity.
DR MalaCards; NHEJ1; -.
DR MIM; 611290; gene.
DR MIM; 611291; phenotype.
DR neXtProt; NX_Q9H9Q4; -.
DR OpenTargets; ENSG00000187736; -.
DR Orphanet; 169079; Cernunnos-XLF deficiency.
DR PharmGKB; PA144596401; -.
DR VEuPathDB; HostDB:ENSG00000187736; -.
DR eggNOG; ENOG502S0R3; Eukaryota.
DR GeneTree; ENSGT00390000009940; -.
DR HOGENOM; CLU_076115_1_0_1; -.
DR InParanoid; Q9H9Q4; -.
DR OMA; CNLMCPL; -.
DR OrthoDB; 1397591at2759; -.
DR PhylomeDB; Q9H9Q4; -.
DR TreeFam; TF328567; -.
DR PathwayCommons; Q9H9Q4; -.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR SignaLink; Q9H9Q4; -.
DR SIGNOR; Q9H9Q4; -.
DR BioGRID-ORCS; 79840; 37 hits in 1084 CRISPR screens.
DR ChiTaRS; NHEJ1; human.
DR EvolutionaryTrace; Q9H9Q4; -.
DR GeneWiki; XLF_(protein); -.
DR GenomeRNAi; 79840; -.
DR Pharos; Q9H9Q4; Tbio.
DR PRO; PR:Q9H9Q4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9H9Q4; protein.
DR Bgee; ENSG00000187736; Expressed in rectum and 130 other tissues.
DR ExpressionAtlas; Q9H9Q4; baseline and differential.
DR Genevisible; Q9H9Q4; HS.
DR GO; GO:0032807; C:DNA ligase IV complex; IBA:GO_Central.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0070419; C:nonhomologous end joining complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0045027; F:DNA end binding; IDA:UniProtKB.
DR GO; GO:0070182; F:DNA polymerase binding; IPI:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; IMP:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; NAS:UniProtKB.
DR GO; GO:0051103; P:DNA ligation involved in DNA repair; IDA:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; IDA:UniProtKB.
DR GO; GO:0051351; P:positive regulation of ligase activity; NAS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; IMP:UniProtKB.
DR Gene3D; 2.170.210.10; -; 1.
DR InterPro; IPR015381; XLF_N.
DR InterPro; IPR038051; XRCC4-like_N_sf.
DR Pfam; PF09302; XLF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosomal rearrangement; Chromosome;
KW Coiled coil; Disease variant; DNA damage; DNA repair; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; SCID.
FT CHAIN 1..299
FT /note="Non-homologous end-joining factor 1"
FT /id="PRO_0000228654"
FT REGION 1..135
FT /note="Globular head"
FT /evidence="ECO:0000305|PubMed:16571728"
FT REGION 255..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 128..170
FT /evidence="ECO:0000269|PubMed:18046455"
FT MOTIF 289..299
FT /note="XLM"
FT /evidence="ECO:0000305|PubMed:27063109"
FT COMPBIAS 255..284
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 115
FT /note="Leu-lock"
FT /evidence="ECO:0000303|PubMed:21775435"
FT MOD_RES 132
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MOD_RES 203
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MOD_RES 245
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MOD_RES 251
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831"
FT MOD_RES 266
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 276..299
FT /note="GTSGPLQRPQLSKVKRKKPRGLFS -> ALCRDLSCQRSRGRSQGVSSVNLL
FT WPQLLRMDLENSFQASP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017689"
FT VARIANT 14
FT /note="A -> T (in dbSNP:rs34689457)"
FT /id="VAR_038790"
FT VARIANT 57
FT /note="R -> G (in NHEJ1-SCID; fails to translocate to the
FT nucleus; dbSNP:rs118204451)"
FT /evidence="ECO:0000269|PubMed:16439204,
FT ECO:0000269|PubMed:17317666"
FT /id="VAR_025704"
FT VARIANT 89
FT /note="H -> R (in dbSNP:rs1056296)"
FT /id="VAR_038791"
FT VARIANT 123
FT /note="C -> R (in NHEJ1-SCID; dbSNP:rs118204452)"
FT /evidence="ECO:0000269|PubMed:16439204"
FT /id="VAR_025705"
FT VARIANT 256
FT /note="Q -> L (in dbSNP:rs35270667)"
FT /id="VAR_038792"
FT MUTAGEN 11
FT /note="Q->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 13
FT /note="W->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 15
FT /note="W->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 24
FT /note="L->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 26
FT /note="K->A: Abolished ability to participate in V(D)J
FT recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 37
FT /note="L->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 40
FT /note="D->A,P: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 41
FT /note="L->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 43
FT /note="Q->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 57
FT /note="R->G: Decreased ability to repair double-strand
FT breaks (DSBs). Impaired ability to participate in V(D)J
FT recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 61
FT /note="L->E: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 64..65
FT /note="RL->ED: Abolished interaction with XRCC4."
FT /evidence="ECO:0000269|PubMed:21775435"
FT MUTAGEN 64
FT /note="R->E: Abolished ability to repair double-strand
FT breaks (DSBs). Abolished interaction with XRCC4. Abolished
FT ability to participate in V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749,
FT ECO:0000269|PubMed:21768349"
FT MUTAGEN 64
FT /note="R->G: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 65
FT /note="L->D: Abolished ability to repair double-strand
FT breaks (DSBs). Abolished ability to participate in V(D)J
FT recombination. Decreased interaction with XRCC4."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 105
FT /note="I->S: Does not affect ability to repair double-
FT strand breaks (DSBs). Does not affect interaction with
FT XRCC4."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 111
FT /note="E->A: Does not affect ability to repair double-
FT strand breaks (DSBs). Does not affect interaction with
FT XRCC4."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 111
FT /note="E->K: Does not affect interaction with XRCC4."
FT /evidence="ECO:0000269|PubMed:21768349"
FT MUTAGEN 115
FT /note="L->A,D: Impaired ability to repair double-strand
FT breaks (DSBs). Abolished interaction with XRCC4. Abolished
FT ability to bridge DNA."
FT /evidence="ECO:0000269|PubMed:18158905,
FT ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:22287571,
FT ECO:0000269|PubMed:26100018"
FT MUTAGEN 115
FT /note="L->D: Abolished ability to repair double-strand
FT breaks (DSBs). Abolished ability to participate in V(D)J
FT recombination. Abolished interaction with XRCC4."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 116
FT /note="P->D: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 117
FT /note="F->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 117
FT /note="F->D: Abolished ability to participate in V(D)J
FT recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 118
FT /note="Y->A,D: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 119
FT /note="W->A: Abolished ability to participate in V(D)J
FT recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 123
FT /note="C->R: Abolished ability to repair double-strand
FT breaks (DSBs). Abolished ability to participate in V(D)J
FT recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 132
FT /note="S->A: In 6A mutant; abolished phosphorylation; does
FT not affect ability to repair double-strand breaks (DSBs),
FT possibly because of redundancy with XRCC4 phosphorylation
FT sites; when associated with A-203, A-245, A-251, A-263 and
FT A-266. In XLF-Ala mutant; abolished phosphorylation by
FT PRKDC; does not affect ability to bridge DNA when
FT associated with XRCC4 phosphorylation-defective mutant;
FT when associated with A-203, A-245 and A-251."
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:28500754"
FT MUTAGEN 132
FT /note="S->D: In XLF-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with XRCC4
FT phospho-mimetic mutant; when associated with D-203, D-245
FT and D-251."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 135
FT /note="L->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 137
FT /note="R->A,N: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 138
FT /note="P->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 139
FT /note="L->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 169
FT /note="E->A: Does not affect ability to repair double-
FT strand breaks (DSBs). Does not affect interaction with
FT XRCC4."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 174
FT /note="L->A: Impaired ability to repair double-strand
FT breaks (DSBs). Does not affect interaction with XRCC4."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 178
FT /note="R->A: Impaired ability to repair double-strand
FT breaks (DSBs). Does not affect interaction with XRCC4. Does
FT not affect ability to participate in V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:18158905,
FT ECO:0000269|PubMed:20558749"
FT MUTAGEN 179
FT /note="L->A: Impaired ability to repair double-strand
FT breaks (DSBs). Does not affect interaction with XRCC4."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 182
FT /note="E->A: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 185
FT /note="E->A: Does not affect ability to repair double-
FT strand breaks (DSBs). Does not affect interaction with
FT XRCC4."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 189..190
FT /note="FL->DD: Does not affect ability to participate in
FT V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20558749"
FT MUTAGEN 195
FT /note="I->A: Does not affect ability to repair double-
FT strand breaks (DSBs). Does not affect interaction with
FT XRCC4."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 203
FT /note="S->A: In 6A mutant; abolished phosphorylation; does
FT not affect ability to repair double-strand breaks (DSBs),
FT possibly because of redundancy with XRCC4 phosphorylation
FT sites; when associated with A-132, A-245, A-251, A-263 and
FT A-266. In XLF-Ala mutant; abolished phosphorylation by
FT PRKDC; does not affect ability to bridge DNA when
FT associated with XRCC4 phosphorylation-defective mutant;
FT when associated with A-132, A-245 and A-251."
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MUTAGEN 203
FT /note="S->D: In XLF-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with XRCC4
FT phospho-mimetic mutant; when associated with D-132, D-245
FT and D-251."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 245
FT /note="S->A: In 6A mutant; abolished phosphorylation; does
FT not affect ability to repair double-strand breaks (DSBs),
FT possibly because of redundancy with XRCC4 phosphorylation
FT sites; when associated with A-132, A-203, A-251, A-263 and
FT A-266. In XLF-Ala mutant; abolished phosphorylation by
FT PRKDC; does not affect ability to bridge DNA when
FT associated with XRCC4 phosphorylation-defective mutant;
FT when associated with A-132, A-203 and A-251."
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MUTAGEN 245
FT /note="S->D: In XLF-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with XRCC4
FT phospho-mimetic mutant; when associated with D-132, D-203
FT and D-251."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 251
FT /note="S->A: In 6A mutant; abolished phosphorylation; does
FT not affect ability to repair double-strand breaks (DSBs),
FT possibly because of redundancy with XRCC4 phosphorylation
FT sites; when associated with A-132, A-203, A-245, A-263 and
FT A-266. In XLF-Ala mutant; abolished phosphorylation by
FT PRKDC; does not affect ability to bridge DNA when
FT associated with XRCC4 phosphorylation-defective mutant;
FT when associated with A-132, A-203 and A-245."
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MUTAGEN 251
FT /note="S->D: In XLF-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with XRCC4
FT phospho-mimetic mutant; when associated with D-132, D-203
FT and D-245."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 263
FT /note="S->A: In 6A mutant; abolished phosphorylation; does
FT not affect ability to repair double-strand breaks (DSBs),
FT possibly because of redundancy with XRCC4 phosphorylation
FT sites; when associated with A-132, A-203, A-245, A-251 and
FT A-266."
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831"
FT MUTAGEN 266
FT /note="T->A: In 6A mutant; abolished phosphorylation; does
FT not affect ability to repair double-strand breaks (DSBs),
FT possibly because of redundancy with XRCC4 phosphorylation
FT sites; when associated with A-132, A-203, A-245, A-251 and
FT A-263."
FT /evidence="ECO:0000269|PubMed:18644470,
FT ECO:0000269|PubMed:22228831"
FT MUTAGEN 278
FT /note="S->A: Does not affect ability to repair double-
FT strand breaks (DSBs). Does not affect interaction with
FT XRCC4."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 293
FT /note="K->A: Abolished DNA-binding."
FT /evidence="ECO:0000269|PubMed:22287571"
FT CONFLICT 256
FT /note="Q -> R (in Ref. 3; CAG33572)"
FT /evidence="ECO:0000305"
FT HELIX 1..9
FT /evidence="ECO:0007829|PDB:2QM4"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:2QM4"
FT STRAND 19..30
FT /evidence="ECO:0007829|PDB:2QM4"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:2QM4"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:2QM4"
FT HELIX 51..61
FT /evidence="ECO:0007829|PDB:2QM4"
FT HELIX 69..85
FT /evidence="ECO:0007829|PDB:2QM4"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:2QM4"
FT STRAND 103..112
FT /evidence="ECO:0007829|PDB:2QM4"
FT STRAND 115..125
FT /evidence="ECO:0007829|PDB:2QM4"
FT HELIX 128..134
FT /evidence="ECO:0007829|PDB:2QM4"
FT HELIX 136..169
FT /evidence="ECO:0007829|PDB:2QM4"
FT HELIX 186..196
FT /evidence="ECO:0007829|PDB:2QM4"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:2QM4"
FT HELIX 208..213
FT /evidence="ECO:0007829|PDB:2QM4"
FT HELIX 215..228
FT /evidence="ECO:0007829|PDB:2QM4"
SQ SEQUENCE 299 AA; 33337 MW; BC5C68076A5E7A96 CRC64;
MEELEQGLLM QPWAWLQLAE NSLLAKVFIT KQGYALLVSD LQQVWHEQVD TSVVSQRAKE
LNKRLTAPPA AFLCHLDNLL RPLLKDAAHP SEATFSCDCV ADALILRVRS ELSGLPFYWN
FHCMLASPSL VSQHLIRPLM GMSLALQCQV RELATLLHMK DLEIQDYQES GATLIRDRLK
TEPFEENSFL EQFMIEKLPE ACSIGDGKPF VMNLQDLYMA VTTQEVQVGQ KHQGAGDPHT
SNSASLQGID SQCVNQPEQL VSSAPTLSAP EKESTGTSGP LQRPQLSKVK RKKPRGLFS
