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 27-MAR-2024, entry version 167. 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 INTERACTION WITH XRCC4 AND LIG4. RX PubMed=22658747; DOI=10.1016/j.str.2012.04.012; RA Ochi T., Wu Q., Chirgadze D.Y., Grossmann J.G., Bolanos-Garcia V.M., RA Blundell T.L.; RT "Structural insights into the role of domain flexibility in human DNA RT ligase IV."; RL Structure 20:1212-1222(2012). RN [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] RP MUTAGENESIS OF LEU-115. RX PubMed=30177755; DOI=10.1038/s41594-018-0120-y; RA Graham T.G.W., Carney S.M., Walter J.C., Loparo J.J.; RT "A single XLF dimer bridges DNA ends during nonhomologous end joining."; RL Nat. Struct. Mol. Biol. 25:877-884(2018). RN [29] RP DOMAIN. RX PubMed=33289484; DOI=10.7554/elife.61920; RA Carney S.M., Moreno A.T., Piatt S.C., Cisneros-Aguirre M., RA Lopezcolorado F.W., Stark J.M., Loparo J.J.; RT "XLF acts as a flexible connector during non-homologous end joining."; RL Elife 9:0-0(2020). RN [30] {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 [31] 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 [32] 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 [33] {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 [34] {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 [35] {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 [36] {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 [37] {ECO:0007744|PDB:7NFC, ECO:0007744|PDB:7NFE} RP STRUCTURE BY ELECTRON MICROSCOPY (4.14 ANGSTROMS) IN COMPLEX WITH THE NHEJ RP COMPLEX AND DNA, AND IDENTIFICATION IN THE NHEJ COMPLEX. RX PubMed=34352203; DOI=10.1016/j.molcel.2021.07.005; RA Chaplin A.K., Hardwick S.W., Stavridi A.K., Buehl C.J., Goff N.J., RA Ropars V., Liang S., De Oliveira T.M., Chirgadze D.Y., Meek K., RA Charbonnier J.B., Blundell T.L.; RT "Cryo-EM of NHEJ supercomplexes provides insights into DNA repair."; RL Mol. Cell 81:3400-3409(2021). RN [38] {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). In some studies, CC has been shown to associate with XRCC4 to form alternating helical CC filaments that bridge DNA and act like a bandage, holding together the CC broken DNA until it is repaired (PubMed:22228831, PubMed:26100018, CC PubMed:28500754, PubMed:27437582, PubMed:21775435, PubMed:22287571, CC PubMed:21768349). Alternatively, it has also been shown that rather CC than forming filaments, a single NHEJ1 dimer interacts through both CC head domains with XRCC4 to promote the close alignment of DNA ends (By CC similarity). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments CC of a DSB in a highly diffusive manner and robustly bridges two CC independent DNA molecules, holding the broken DNA fragments in close CC proximity to one other (PubMed:28500754, PubMed:27437582). The mobility CC of the bridges ensures that the ends remain accessible for further CC processing by other repair factors (PubMed:27437582). Binds DNA in a CC length-dependent manner (PubMed:17317666, PubMed:18158905). CC {ECO:0000250|UniProtKB:A0A1L8ENT6, 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 PubMed:22658747). Component of the core long-range non-homologous end CC joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, CC LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:16571728, CC PubMed:17317666, PubMed:33854234, PubMed:34352203). Additional CC component of the NHEJ complex includes PAXX (PubMed:25574025, CC PubMed:25941166). Following autophosphorylation, PRKDC dissociates from CC DNA, leading to formation of the short-range NHEJ complex, composed of CC LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:33854234). CC Interacts with POLL (DNA polymerase lambda); promoting POLL recruitment CC to double-strand breaks (DSBs) and stimulation of the end-filling CC activity of POLL (PubMed:30250067). {ECO:0000269|PubMed:16439205, CC ECO:0000269|PubMed:16571728, ECO:0000269|PubMed:17317666, CC ECO:0000269|PubMed:18046455, ECO:0000269|PubMed:18158905, CC ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:21768349, CC ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:21936820, CC ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, CC ECO:0000269|PubMed:22658747, 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 ECO:0000269|PubMed:34352203}. 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 -!- DOMAIN: The XLM motif (also called the KBM motif or KBMX motif) and the CC interior region of the C-terminal tail preceding the XLM motif are CC essential for DNA end joining (PubMed:33289484). The sequence of the C- CC terminal tail is not critical for its role in end joining but it must CC be sufficiently long to interact with XRCC4 and to stabilize the CC interaction of XRCC4 with LIG4 (By similarity). A single XLM motif and CC C-terminal tail is sufficient to promote end joining (By similarity). CC {ECO:0000250|UniProtKB:A0A1L8ENT6, ECO:0000269|PubMed:33289484}. 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7ZYG; EM; 2.68 A; F=1-299. DR PDB; 8BHV; EM; 4.51 A; Q/R=1-299. DR PDB; 8BHY; EM; 5.33 A; f/m=1-299. DR PDB; 8BOT; EM; 7.76 A; Q/R/X/Y=1-299. DR PDB; 8EZA; EM; 4.39 A; H/I=1-299. DR PDB; 8EZB; EM; 8.90 A; H/I=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 PDBsum; 7ZYG; -. DR PDBsum; 8BHV; -. DR PDBsum; 8BHY; -. DR PDBsum; 8BOT; -. DR PDBsum; 8EZA; -. DR PDBsum; 8EZB; -. DR AlphaFoldDB; Q9H9Q4; -. DR EMDB; EMD-12299; -. DR EMDB; EMD-12301; -. DR EMDB; EMD-15022; -. DR EMDB; EMD-16070; -. DR EMDB; EMD-16074; -. DR EMDB; EMD-16145; -. DR EMDB; EMD-23509; -. DR EMDB; EMD-23510; -. DR EMDB; EMD-23512; -. DR EMDB; EMD-23515; -. DR EMDB; EMD-28732; -. DR EMDB; EMD-28733; -. DR EMDB; EMD-28736; -. DR EMDB; EMD-28739; -. DR SMR; Q9H9Q4; -. DR BioGRID; 122931; 18. 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; 9606-ENSP00000349313; -. DR PeptideAtlas; Q9H9Q4; -. DR ProteomicsDB; 81350; -. [Q9H9Q4-1] DR ProteomicsDB; 81351; -. [Q9H9Q4-2] DR Pumba; Q9H9Q4; -. DR Antibodypedia; 34300; 538 antibodies from 32 providers. DR DNASU; 79840; -. DR Ensembl; ENST00000356853.10; ENSP00000349313.5; ENSG00000187736.14. [Q9H9Q4-1] DR Ensembl; ENST00000409720.5; ENSP00000387290.1; ENSG00000187736.14. [Q9H9Q4-2] DR Ensembl; ENST00000457600.3; ENSP00000407201.2; ENSG00000187736.14. [Q9H9Q4-1] DR Ensembl; ENST00000698174.1; ENSP00000513594.1; ENSG00000187736.14. [Q9H9Q4-1] DR Ensembl; ENST00000698202.1; ENSP00000513605.1; ENSG00000187736.14. [Q9H9Q4-1] DR Ensembl; ENST00000698203.1; ENSP00000513606.1; ENSG00000187736.14. [Q9H9Q4-1] 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 AGR; HGNC:25737; -. 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; VTRQEIQ; -. DR OrthoDB; 5390247at2759; -. 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; 38 hits in 1162 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 132 other cell types or tissues. DR ExpressionAtlas; Q9H9Q4; baseline and differential. DR GO; GO:0032807; C:DNA ligase IV complex; IBA:GO_Central. DR GO; GO:0005958; C:DNA-dependent protein kinase-DNA ligase 4 complex; IDA:UniProtKB. 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 CDD; cd22210; HD_XRCC4-like_N; 1. DR Gene3D; 2.170.210.10; DNA double-strand break repair and VJ recombination XRCC4, N-terminal; 1. DR Gene3D; 1.10.287.450; Helix hairpin bin; 1. DR InterPro; IPR015381; XLF_N. DR InterPro; IPR038051; XRCC4-like_N_sf. DR PANTHER; PTHR32235; NON-HOMOLOGOUS END-JOINING FACTOR 1; 1. DR PANTHER; PTHR32235:SF1; NON-HOMOLOGOUS END-JOINING FACTOR 1; 1. DR Pfam; PF09302; XLF; 1. DR Genevisible; Q9H9Q4; HS. 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 224..288 FT /note="C-terminal tail" FT /evidence="ECO:0000250|UniProtKB:A0A1L8ENT6" 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 FT double-strand breaks (DSBs). Does not affect interaction FT with XRCC4." FT /evidence="ECO:0000269|PubMed:18158905" FT MUTAGEN 111 FT /note="E->A: Does not affect ability to repair FT double-strand breaks (DSBs). Does not affect interaction FT with 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: Impaired ability to repair double-strand FT breaks (DSBs). Abolished ability to bridge DNA. Some FT studies show lack of interaction with XRCC4 while another FT shows that this mutant retains the ability to interact with FT XRCC4." FT /evidence="ECO:0000269|PubMed:18158905, FT ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:22287571, FT ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:30177755" FT MUTAGEN 115 FT /note="L->D: Impaired ability to repair double-strand FT breaks (DSBs). Abolished ability to bridge DNA. Abolished FT ability to participate in V(D)J recombination. Abolished FT interaction with XRCC4." FT /evidence="ECO:0000269|PubMed:18158905, FT ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:21775435, FT ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:26100018" 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 FT double-strand breaks (DSBs). Does not affect interaction FT with 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 FT double-strand breaks (DSBs). Does not affect interaction FT with 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 FT double-strand breaks (DSBs). Does not affect interaction FT with 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 FT double-strand breaks (DSBs). Does not affect interaction FT with 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" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:7ZYG" 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 //