XRCC4_HUMAN
ID XRCC4_HUMAN Reviewed; 336 AA.
AC Q13426; A8K3X4; Q9BS72; Q9UP94;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=DNA repair protein XRCC4 {ECO:0000305};
DE Short=hXRCC4 {ECO:0000303|PubMed:14599745};
DE AltName: Full=X-ray repair cross-complementing protein 4 {ECO:0000303|PubMed:8548796};
DE Contains:
DE RecName: Full=Protein XRCC4, C-terminus {ECO:0000305|PubMed:33725486};
DE Short=XRCC4/C {ECO:0000303|PubMed:33725486};
GN Name=XRCC4 {ECO:0000303|PubMed:8548796, ECO:0000312|HGNC:HGNC:12831};
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 2), FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8548796; DOI=10.1016/0092-8674(95)90135-3;
RA Li Z., Otevrel T., Gao Y., Cheng H.L., Seed B., Stamato T.D.,
RA Taccioli G.E., Alt F.W.;
RT "The XRCC4 gene encodes a novel protein involved in DNA double-strand break
RT repair and V(D)J recombination.";
RL Cell 83:1079-1089(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Fugmann S.D., Schwarz K.;
RT "The genomic structure of the human XRCC4 gene.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Tatsumi K.;
RT "Human lymphoblastoid cell line TK-6 lacking in a novel component involved
RT in V(D)J recombination.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-12; THR-56; THR-134;
RP GLN-142 AND SER-247.
RG NIEHS SNPs program;
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Bone marrow;
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 [9]
RP INTERACTION WITH LIG4, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=9259561; DOI=10.1016/s0960-9822(06)00258-2;
RA Critchlow S.E., Bowater R.P., Jackson S.P.;
RT "Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA
RT ligase IV.";
RL Curr. Biol. 7:588-598(1997).
RN [10]
RP PHOSPHORYLATION BY PRKDC.
RX PubMed=9430729; DOI=10.1074/jbc.273.3.1794;
RA Leber R., Wise T.W., Mizuta R., Meek K.;
RT "The XRCC4 gene product is a target for and interacts with the DNA-
RT dependent protein kinase.";
RL J. Biol. Chem. 273:1794-1801(1998).
RN [11]
RP PHOSPHORYLATION AT SER-260 AND SER-320.
RX PubMed=15177042; DOI=10.1016/j.dnarep.2003.11.005;
RA Lee K.J., Jovanovic M., Udayakumar D., Bladen C.L., Dynan W.S.;
RT "Identification of DNA-PKcs phosphorylation sites in XRCC4 and effects of
RT mutations at these sites on DNA end joining in a cell-free system.";
RL DNA Repair 3:267-276(2004).
RN [12]
RP FUNCTION, AND INTERACTION WITH LIG4.
RX PubMed=9242410; DOI=10.1038/41358;
RA Grawunder U., Wilm M., Wu X., Kulesza P., Wilson T.E., Mann M.,
RA Lieber M.R.;
RT "Activity of DNA ligase IV stimulated by complex formation with XRCC4
RT protein in mammalian cells.";
RL Nature 388:492-495(1997).
RN [13]
RP PROTEOLYTIC CLEAVAGE, AND PHOSPHORYLATION.
RX PubMed=10922471; DOI=10.1016/s0014-5793(00)01800-7;
RA Matsumoto Y., Suzuki N., Namba N., Umeda N., Ma X.J., Morita A., Tomita M.,
RA Enomoto A., Serizawa S., Hirano K., Sakaia K., Yasuda H., Hosoi Y.;
RT "Cleavage and phosphorylation of XRCC4 protein induced by X-irradiation.";
RL FEBS Lett. 478:67-71(2000).
RN [14]
RP FUNCTION, AND INTERACTION WITH LIG4; XRCC6; XRCC5 AND PRKDC.
RX PubMed=10854421; DOI=10.1074/jbc.m000491200;
RA Chen L., Trujillo K., Sung P., Tomkinson A.E.;
RT "Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-
RT dependent protein kinase.";
RL J. Biol. Chem. 275:26196-26205(2000).
RN [15]
RP FUNCTION, AND INTERACTION WITH XRCC6 AND XRCC5.
RX PubMed=10757784; DOI=10.1128/mcb.20.9.2996-3003.2000;
RA Nick McElhinny S.A., Snowden C.M., McCarville J., Ramsden D.A.;
RT "Ku recruits the XRCC4-ligase IV complex to DNA ends.";
RL Mol. Cell. Biol. 20:2996-3003(2000).
RN [16]
RP INTERACTION WITH PRKDC.
RX PubMed=12509254; DOI=10.1016/s1568-7864(01)00018-0;
RA Hsu H.-L., Yannone S.M., Chen D.J.;
RT "Defining interactions between DNA-PK and ligase IV/XRCC4.";
RL DNA Repair 1:225-235(2002).
RN [17]
RP FUNCTION, AND INTERACTION WITH LIG4.
RX PubMed=12517771;
RA Lee J.W., Yannone S.M., Chen D.J., Povirk L.F.;
RT "Requirement for XRCC4 and DNA ligase IV in alignment-based gap filling for
RT nonhomologous DNA end joining in vitro.";
RL Cancer Res. 63:22-24(2003).
RN [18]
RP PHOSPHORYLATION AT SER-53; SER-193; SER-260; SER-303; SER-315; SER-320;
RP THR-323; SER-327 AND SER-328, AND MUTAGENESIS OF SER-260 AND SER-320.
RX PubMed=14599745; DOI=10.1016/s1568-7864(03)00143-5;
RA Yu Y., Wang W., Ding Q., Ye R., Chen D., Merkle D., Schriemer D., Meek K.,
RA Lees-Miller S.P.;
RT "DNA-PK phosphorylation sites in XRCC4 are not required for survival after
RT radiation or for V(D)J recombination.";
RL DNA Repair 2:1239-1252(2003).
RN [19]
RP IDENTIFICATION IN A COMPLEX WITH XRCC6; XRCC5 AND PRKDC, AND
RP PHOSPHORYLATION.
RX PubMed=12547193; DOI=10.1016/s0022-2836(02)01328-1;
RA Calsou P., Delteil C., Frit P., Drouet J., Salles B.;
RT "Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein
RT kinase on DNA ends is necessary for XRCC4-ligase IV recruitment.";
RL J. Mol. Biol. 326:93-103(2003).
RN [20]
RP INTERACTION WITH APTX, AND PHOSPHORYLATION.
RX PubMed=15380105; DOI=10.1016/j.dnarep.2004.06.017;
RA Clements P.M., Breslin C., Deeks E.D., Byrd P.J., Ju L., Bieganowski P.,
RA Brenner C., Moreira M.-C., Taylor A.M.R., Caldecott K.W.;
RT "The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM
RT and interacts with the DNA strand break repair proteins XRCC1 and XRCC4.";
RL DNA Repair 3:1493-1502(2004).
RN [21]
RP FUNCTION, PHOSPHORYLATION AT THR-233, INTERACTION WITH PNKP, AND
RP MUTAGENESIS OF THR-233; THR-264; THR-282; THR-308 AND THR-323.
RX PubMed=15385968; DOI=10.1038/sj.emboj.7600375;
RA Koch C.A., Agyei R., Galicia S., Metalnikov P., O'Donnell P.,
RA Starostine A., Weinfeld M., Durocher D.;
RT "Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA
RT ligation by DNA ligase IV.";
RL EMBO J. 23:3874-3885(2004).
RN [22]
RP MONOUBIQUITINATION, PHOSPHORYLATION, AND FUNCTION.
RX PubMed=16412978; DOI=10.1016/j.bbrc.2005.12.166;
RA Foster R.E., Nnakwe C., Woo L., Frank K.M.;
RT "Monoubiquitination of the nonhomologous end joining protein XRCC4.";
RL Biochem. Biophys. Res. Commun. 341:175-183(2006).
RN [23]
RP INTERACTION WITH NHEJ1.
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 [24]
RP FUNCTION, AND INTERACTION WITH XRCC6.
RX PubMed=17124166; DOI=10.1073/pnas.0609061103;
RA Mari P.O., Florea B.I., Persengiev S.P., Verkaik N.S., Brueggenwirth H.T.,
RA Modesti M., Giglia-Mari G., Bezstarosti K., Demmers J.A., Luider T.M.,
RA Houtsmuller A.B., van Gent D.C.;
RT "Dynamic assembly of end-joining complexes requires interaction between
RT Ku70/80 and XRCC4.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:18597-18602(2006).
RN [25]
RP SUMOYLATION AT LYS-210, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-140
RP AND LYS-210.
RX PubMed=16478998; DOI=10.1128/mcb.26.5.1786-1794.2006;
RA Yurchenko V., Xue Z., Sadofsky M.J.;
RT "SUMO modification of human XRCC4 regulates its localization and function
RT in DNA double-strand break repair.";
RL Mol. Cell. Biol. 26:1786-1794(2006).
RN [26]
RP FUNCTION, AND INTERACTION WITH LIG4.
RX PubMed=17290226; DOI=10.1038/sj.emboj.7601559;
RA Gu J., Lu H., Tippin B., Shimazaki N., Goodman M.F., Lieber M.R.;
RT "XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across
RT gaps.";
RL EMBO J. 26:1010-1023(2007).
RN [27]
RP INTERACTION WITH NHEJ1, AND MUTAGENESIS OF LYS-4; LYS-26; LYS-65; ARG-71;
RP LYS-72; LYS-99 AND LYS-102.
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 INTERACTION WITH APLF.
RX PubMed=17396150; DOI=10.1038/sj.emboj.7601663;
RA Kanno S., Kuzuoka H., Sasao S., Hong Z., Lan L., Nakajima S., Yasui A.;
RT "A novel human AP endonuclease with conserved zinc-finger-like motifs
RT involved in DNA strand break responses.";
RL EMBO J. 26:2094-2103(2007).
RN [29]
RP INTERACTION WITH APLF.
RX PubMed=17353262; DOI=10.1128/mcb.02269-06;
RA Iles N., Rulten S., El-Khamisy S.F., Caldecott K.W.;
RT "APLF (C2orf13) is a novel human protein involved in the cellular response
RT to chromosomal DNA strand breaks.";
RL Mol. Cell. Biol. 27:3793-3803(2007).
RN [30]
RP INTERACTION WITH APLF.
RX PubMed=18077224; DOI=10.1016/j.dnarep.2007.10.008;
RA Macrae C.J., McCulloch R.D., Ylanko J., Durocher D., Koch C.A.;
RT "APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-
RT dependent hyperphosphorylation following ionizing radiation.";
RL DNA Repair 7:292-302(2008).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-327 AND SER-328, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [32]
RP INTERACTION WITH LIG4.
RX PubMed=19837014; DOI=10.1016/j.dnarep.2009.09.007;
RA Recuero-Checa M.A., Dore A.S., Arias-Palomo E., Rivera-Calzada A.,
RA Scheres S.H., Maman J.D., Pearl L.H., Llorca O.;
RT "Electron microscopy of Xrcc4 and the DNA ligase IV-Xrcc4 DNA repair
RT complex.";
RL DNA Repair 8:1380-1389(2009).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-327 AND SER-328, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [34]
RP INTERACTION WITH NHEJ1.
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 [35]
RP FUNCTION, PHOSPHORYLATION AT THR-233, AND INTERACTION WITH PNKP.
RX PubMed=20852255; DOI=10.1074/jbc.m109.058719;
RA Mani R.S., Yu Y., Fang S., Lu M., Fanta M., Zolner A.E., Tahbaz N.,
RA Ramsden D.A., Litchfield D.W., Lees-Miller S.P., Weinfeld M.;
RT "Dual modes of interaction between XRCC4 and polynucleotide
RT kinase/phosphatase: implications for nonhomologous end joining.";
RL J. Biol. Chem. 285:37619-37629(2010).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [37]
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 [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [39]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH LIG4.
RX PubMed=21982441; DOI=10.1016/j.dnarep.2011.09.012;
RA Berg E., Christensen M.O., Dalla Rosa I., Wannagat E., Jaenicke R.U.,
RA Roesner L.M., Dirks W.G., Boege F., Mielke C.;
RT "XRCC4 controls nuclear import and distribution of Ligase IV and exchanges
RT faster at damaged DNA in complex with Ligase IV.";
RL DNA Repair 10:1232-1242(2011).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [41]
RP FUNCTION, INTERACTION WITH NHEJ1, AND PHOSPHORYLATION AT SER-193; SER-260;
RP SER-303; SER-315; SER-320; THR-323; SER-327 AND SER-328.
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 [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-260; SER-304 AND SER-320, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [43]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LIG4.
RX PubMed=24984242; DOI=10.1016/j.dnarep.2014.05.010;
RA Francis D.B., Kozlov M., Chavez J., Chu J., Malu S., Hanna M., Cortes P.;
RT "DNA Ligase IV regulates XRCC4 nuclear localization.";
RL DNA Repair 21:36-42(2014).
RN [44]
RP INVOLVEMENT IN SSMED, AND VARIANT SSMED ARG-43.
RX PubMed=24389050; DOI=10.1101/gr.160572.113;
RA Shaheen R., Faqeih E., Ansari S., Abdel-Salam G., Al-Hassnan Z.N.,
RA Al-Shidi T., Alomar R., Sogaty S., Alkuraya F.S.;
RT "Genomic analysis of primordial dwarfism reveals novel disease genes.";
RL Genome Res. 24:291-299(2014).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-229; THR-233 AND SER-237, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [46]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-235; GLU-322;
RP THR-323; LEU-324; ASN-326; SER-327; SER-328; PRO-329; GLU-330; ASP-331;
RP LEU-332; PHE-333 AND ASP-334.
RX PubMed=25597996; DOI=10.1016/j.bbrc.2015.01.015;
RA Wanotayan R., Fukuchi M., Imamichi S., Sharma M.K., Matsumoto Y.;
RT "Asparagine 326 in the extremely C-terminal region of XRCC4 is essential
RT for the cell survival after irradiation.";
RL Biochem. Biophys. Res. Commun. 457:526-531(2015).
RN [47]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LIG4, NUCLEAR LOCALIZATION
RP SIGNAL, AND MUTAGENESIS OF LYS-210 AND LYS-271.
RX PubMed=25934149; DOI=10.1016/j.bbrc.2015.04.093;
RA Fukuchi M., Wanotayan R., Liu S., Imamichi S., Sharma M.K., Matsumoto Y.;
RT "Lysine 271 but not lysine 210 of XRCC4 is required for the nuclear
RT localization of XRCC4 and DNA ligase IV.";
RL Biochem. Biophys. Res. Commun. 461:687-694(2015).
RN [48]
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 [49]
RP FUNCTION, AND INTERACTION WITH NHEJ1.
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 [50]
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 [51]
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 [52]
RP PHOSPHORYLATION AT SER-320.
RX PubMed=26666690; DOI=10.1093/jrr/rrv086;
RA Sharma M.K., Imamichi S., Fukuchi M., Samarth R.M., Tomita M.,
RA Matsumoto Y.;
RT "In cellulo phosphorylation of XRCC4 Ser320 by DNA-PK induced by DNA
RT damage.";
RL J. Radiat. Res. 57:115-120(2016).
RN [53]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH XRCC5 AND XRCC6,
RP PHOSPHORYLATION AT SER-327 AND SER-328, UBIQUITINATION AT LYS-296, AND
RP MUTAGENESIS OF LYS-271; LYS-285; LYS-296; THR-308 AND 327-SER-SER-328.
RX PubMed=26774286; DOI=10.1016/j.molcel.2015.12.010;
RA Zhang Q., Karnak D., Tan M., Lawrence T.S., Morgan M.A., Sun Y.;
RT "FBXW7 facilitates nonhomologous end-joining via K63-linked
RT polyubiquitylation of XRCC4.";
RL Mol. Cell 61:419-433(2016).
RN [54]
RP FUNCTION, INTERACTION WITH NHEJ1, 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 [55]
RP FUNCTION, PHOSPHORYLATION AT SER-193; SER-260; SER-304; SER-315; SER-320;
RP THR-323; SER-327 AND SER-328, AND MUTAGENESIS OF SER-193; SER-260; SER-304;
RP SER-315; SER-320; THR-323; SER-327 AND SER-328.
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 [56]
RP FUNCTION, PHOSPHORYLATION AT SER-232 AND THR-233, AND INTERACTION WITH
RP PNKP.
RX PubMed=28453785; DOI=10.1093/nar/gkx275;
RA Aceytuno R.D., Piett C.G., Havali-Shahriari Z., Edwards R.A., Rey M.,
RA Ye R., Javed F., Fang S., Mani R., Weinfeld M., Hammel M., Tainer J.A.,
RA Schriemer D.C., Lees-Miller S.P., Glover J.N.M.;
RT "Structural and functional characterization of the PNKP-XRCC4-LigIV DNA
RT repair complex.";
RL Nucleic Acids Res. 45:6238-6251(2017).
RN [57]
RP PHOSPHORYLATION AT SER-260, AND MUTAGENESIS OF SER-260.
RX PubMed=30247612; DOI=10.1093/jrr/rry072;
RA Amiri Moghani A.R., Sharma M.K., Matsumoto Y.;
RT "In cellulo phosphorylation of DNA double-strand break repair protein XRCC4
RT on Ser260 by DNA-PK.";
RL J. Radiat. Res. 59:700-708(2018).
RN [58]
RP 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 [59]
RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF
RP 262-ASP--ASP-265; ILE-266; ARG-270; LYS-271; ARG-272; ARG-273 AND ARG-275.
RX PubMed=33725486; DOI=10.1016/j.molcel.2021.02.025;
RA Maruoka M., Zhang P., Mori H., Imanishi E., Packwood D.M., Harada H.,
RA Kosako H., Suzuki J.;
RT "Caspase cleavage releases a nuclear protein fragment that stimulates
RT phospholipid scrambling at the plasma membrane.";
RL Mol. Cell 81:1397-1410(2021).
RN [60] {ECO:0007744|PDB:1FU1}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-203, AND SUBUNIT.
RX PubMed=11080143; DOI=10.1093/emboj/19.22.5962;
RA Junop M.S., Modesti M., Guarne A., Ghirlando R., Gellert M., Yang W.;
RT "Crystal structure of the Xrcc4 DNA repair protein and implications for end
RT joining.";
RL EMBO J. 19:5962-5970(2000).
RN [61]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-113 IN COMPLEX WITH LIG4.
RX PubMed=11702069; DOI=10.1038/nsb725;
RA Sibanda B.L., Critchlow S.E., Begun J., Pei X.Y., Jackson S.P.,
RA Blundell T.L., Pellegrini L.;
RT "Crystal structure of an Xrcc4-DNA ligase IV complex.";
RL Nat. Struct. Biol. 8:1015-1019(2001).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-203.
RX PubMed=14607114; DOI=10.1016/j.jmb.2003.09.031;
RA Modesti M., Junop M.S., Ghirlando R., van de Rakt M., Gellert M., Yang W.,
RA Kanaar R.;
RT "Tetramerization and DNA ligase IV interaction of the DNA double-strand
RT break repair protein XRCC4 are mutually exclusive.";
RL J. Mol. Biol. 334:215-228(2003).
RN [63] {ECO:0007744|PDB:3II6}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-203 IN COMPLEX WITH LIG4, AND
RP INTERACTION WITH LIG4.
RX PubMed=19332554; DOI=10.1128/mcb.01895-08;
RA Wu P.Y., Frit P., Meesala S., Dauvillier S., Modesti M., Andres S.N.,
RA Huang Y., Sekiguchi J., Calsou P., Salles B., Junop M.S.;
RT "Structural and functional interaction between the human DNA repair
RT proteins DNA ligase IV and XRCC4.";
RL Mol. Cell. Biol. 29:3163-3172(2009).
RN [64] {ECO:0007744|PDB:3W03}
RP X-RAY CRYSTALLOGRAPHY (8.49 ANGSTROMS) OF 1-164 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 [65] {ECO:0007744|PDB:3SR2}
RP X-RAY CRYSTALLOGRAPHY (3.97 ANGSTROMS) OF 1-140 IN COMPLEX WITH NHEJ1,
RP FUNCTION, AND INTERACTION WITH NHEJ1.
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 [66] {ECO:0007744|PDB:3RWR}
RP X-RAY CRYSTALLOGRAPHY (3.94 ANGSTROMS) OF 1-157 IN COMPLEX WITH NHEJ1,
RP FUNCTION, INTERACTION WITH NHEJ1, AND MUTAGENESIS OF LYS-65; LYS-72;
RP LYS-90; LYS-99; GLU-170 AND ARG-192.
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 [67] {ECO:0007744|PDB:3Q4F}
RP X-RAY CRYSTALLOGRAPHY (5.50 ANGSTROMS) OF 1-157 IN COMPLEX WITH NHEJ1,
RP FUNCTION, INTERACTION WITH NHEJ1, AND MUTAGENESIS OF GLU-55; ASP-58;
RP MET-61; GLU-62; LYS-65; GLU-69 AND PHE-106.
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 [68] {ECO:0007744|PDB:6ABO}
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1-213, SUBUNIT, INTERACTION WITH
RP IFFO1, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=31548606; DOI=10.1038/s41556-019-0388-0;
RA Li W., Bai X., Li J., Zhao Y., Liu J., Zhao H., Liu L., Ding M., Wang Q.,
RA Shi F.Y., Hou M., Ji J., Gao G., Guo R., Sun Y., Liu Y., Xu D.;
RT "The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses
RT chromosome translocation during tumorigenesis.";
RL Nat. Cell Biol. 21:1273-1285(2019).
RN [69] {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).
RN [70]
RP VARIANTS SSMED ARG-43; 161-ARG--ILE-336 DEL; 225-ARG--ILE-336 DEL AND
RP 275-ARG--ILE-336 DEL.
RX PubMed=25728776; DOI=10.1016/j.ajhg.2015.01.013;
RA Murray J.E., van der Burg M., Ijspeert H., Carroll P., Wu Q., Ochi T.,
RA Leitch A., Miller E.S., Kysela B., Jawad A., Bottani A., Brancati F.,
RA Cappa M., Cormier-Daire V., Deshpande C., Faqeih E.A., Graham G.E.,
RA Ranza E., Blundell T.L., Jackson A.P., Stewart G.S., Bicknell L.S.;
RT "Mutations in the NHEJ component XRCC4 cause primordial dwarfism.";
RL Am. J. Hum. Genet. 96:412-424(2015).
RN [71]
RP VARIANT SSMED 225-ARG--ILE-336 DEL.
RX PubMed=25872942; DOI=10.15252/emmm.201404803;
RA Bee L., Nasca A., Zanolini A., Cendron F., d'Adamo P., Costa R.,
RA Lamperti C., Celotti L., Ghezzi D., Zeviani M.;
RT "A nonsense mutation of human XRCC4 is associated with adult-onset
RT progressive encephalocardiomyopathy.";
RL EMBO Mol. Med. 7:918-929(2015).
RN [72]
RP VARIANTS SSMED GLN-161 AND 275-ARG--ILE-336 DEL, AND CHARACTERIZATION OF
RP VARIANT SSMED GLN-161.
RX PubMed=25839420; DOI=10.1093/hmg/ddv115;
RA Rosin N., Elcioglu N.H., Beleggia F., Isgueven P., Altmueller J.,
RA Thiele H., Steindl K., Joset P., Rauch A., Nuernberg P., Wollnik B.,
RA Yigit G.;
RT "Mutations in XRCC4 cause primary microcephaly, short stature and increased
RT genomic instability.";
RL Hum. Mol. Genet. 24:3708-3717(2015).
RN [73]
RP VARIANTS SSMED ARG-43 AND 225-ARG--ILE-336 DEL, AND CHARACTERIZATION OF
RP VARIANT SSMED ARG-43.
RX PubMed=26255102; DOI=10.1016/j.jaci.2015.06.007;
RA Guo C., Nakazawa Y., Woodbine L., Bjoerkman A., Shimada M., Fawcett H.,
RA Jia N., Ohyama K., Li T.S., Nagayama Y., Mitsutake N., Pan-Hammarstroem Q.,
RA Gennery A.R., Lehmann A.R., Jeggo P.A., Ogi T.;
RT "XRCC4 deficiency in human subjects causes a marked neurological phenotype
RT but no overt immunodeficiency.";
RL J. Allergy Clin. Immunol. 136:1007-1017(2015).
RN [74]
RP VARIANT SSMED GLU-82, CHARACTERIZATION OF VARIANT SSMED GLU-82, AND
RP FUNCTION.
RX PubMed=25742519; DOI=10.1210/jc.2015-1098;
RA de Bruin C., Mericq V., Andrew S.F., van Duyvenvoorde H.A., Verkaik N.S.,
RA Losekoot M., Porollo A., Garcia H., Kuang Y., Hanson D., Clayton P.,
RA van Gent D.C., Wit J.M., Hwa V., Dauber A.;
RT "An XRCC4 splice mutation associated with severe short stature, gonadal
RT failure, and early-onset metabolic syndrome.";
RL J. Clin. Endocrinol. Metab. 100:E789-E798(2015).
RN [75]
RP VARIANT SSMED 210-LYS--ILE-336 DEL.
RX PubMed=32524007; DOI=10.4158/accr-2019-0283;
RA Fredette M.E., Lombardi K.C., Duker A.L., Buck C.O., Phornphutkul C.,
RA Bober M.B., Quintos J.B.;
RT "Novel XRCC4 mutations in an infant with microcephalic primordial dwarfism,
RT dilated cardiomyopathy, subclinical hypothyroidism, and early death:
RT expanding the phenotype of XRCC4 mutations.";
RL AACE Clin. Case Rep. 6:e1-e4(2020).
CC -!- FUNCTION: [DNA repair protein XRCC4]: DNA non-homologous end joining
CC (NHEJ) core factor, required for double-strand break repair and V(D)J
CC recombination (PubMed:10757784, PubMed:10854421, PubMed:17124166,
CC PubMed:16412978, PubMed:8548796, PubMed:25742519, PubMed:12517771,
CC PubMed:17290226, PubMed:22228831, PubMed:25597996, PubMed:25934149,
CC PubMed:26100018, PubMed:26774286). Acts as a scaffold protein that
CC regulates recruitment of other proteins to DNA double-strand breaks
CC (DSBs) (PubMed:15385968, PubMed:20852255, PubMed:26774286,
CC PubMed:27437582). Associates with NHEJ1/XLF 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:26100018, PubMed:27437582,
CC PubMed:28500754, PubMed:21775435, PubMed:22287571, PubMed:21768349).
CC The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a
CC highly diffusive manner and robustly bridges two independent DNA
CC molecules, holding the broken DNA fragments in close proximity to one
CC other (PubMed:27437582). The mobility of the bridges ensures that the
CC ends remain accessible for further processing by other repair factors
CC (PubMed:27437582). Plays a key role in the NHEJ ligation step of the
CC broken DNA during DSB repair via direct interaction with DNA ligase IV
CC (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap
CC filling is completed (PubMed:9242410, PubMed:10757784, PubMed:10854421,
CC PubMed:12517771, PubMed:17290226, PubMed:19837014). XRCC4 stabilizes
CC LIG4, regulates its subcellular localization and enhances LIG4's
CC joining activity (PubMed:9242410, PubMed:10757784, PubMed:10854421,
CC PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:22228831).
CC Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the
CC assembly of the DNA-dependent protein kinase complex DNA-PK to these
CC DNA ends (PubMed:10757784, PubMed:10854421). Promotes displacement of
CC PNKP from processed strand break termini (PubMed:20852255,
CC PubMed:28453785). {ECO:0000269|PubMed:10757784,
CC ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771,
CC ECO:0000269|PubMed:15385968, ECO:0000269|PubMed:16412978,
CC ECO:0000269|PubMed:17124166, ECO:0000269|PubMed:17290226,
CC ECO:0000269|PubMed:19837014, ECO:0000269|PubMed:20852255,
CC ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435,
CC ECO:0000269|PubMed:21982441, ECO:0000269|PubMed:22228831,
CC ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25597996,
CC ECO:0000269|PubMed:25742519, ECO:0000269|PubMed:25934149,
CC ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:26774286,
CC ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28453785,
CC ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:8548796,
CC ECO:0000269|PubMed:9242410}.
CC -!- FUNCTION: [Protein XRCC4, C-terminus]: Acts as an activator of the
CC phospholipid scramblase activity of XKR4 (PubMed:33725486). This form,
CC which is generated upon caspase-3 (CASP3) cleavage, translocates into
CC the cytoplasm and interacts with XKR4, thereby promoting
CC phosphatidylserine scramblase activity of XKR4 and leading to
CC phosphatidylserine exposure on apoptotic cell surface
CC (PubMed:33725486). {ECO:0000269|PubMed:33725486}.
CC -!- SUBUNIT: [DNA repair protein XRCC4]: Homodimer and homotetramer in
CC solution (PubMed:25574025, PubMed:25670504, PubMed:25941166,
CC PubMed:31548606, PubMed:11080143). Interacts with NHEJ1/XLF; the
CC interaction is direct and is mediated via a head-to-head interaction
CC between N-terminal head regions (PubMed:16439205, PubMed:18158905,
CC PubMed:20558749, PubMed:22228831, PubMed:26100018, PubMed:27437582,
CC PubMed:21936820, PubMed:21775435, PubMed:22287571, PubMed:21768349).
CC Interacts with LIG4; the LIG4-XRCC4 subcomplex has a 1:2 stoichiometry
CC and XRCC4 is required for LIG4 stability (PubMed:9259561,
CC PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:24984242,
CC PubMed:25934149, PubMed:11702069, PubMed:19332554, PubMed:9242410).
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:10757784, PubMed:10854421,
CC PubMed:17124166, PubMed:12547193, PubMed:26774286, PubMed:33854234).
CC Additional component of the NHEJ complex includes PAXX
CC (PubMed:16439205). Following autophosphorylation, PRKDC dissociates
CC from DNA, leading to formation of the short-range NHEJ complex,
CC composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF
CC (PubMed:33854234). Interacts with PRKDC; the interaction is direct
CC (PubMed:12509254). Interacts with XRCC6/Ku70; the interaction is direct
CC (PubMed:17124166). Interacts with APTX and APLF (PubMed:15380105,
CC PubMed:17396150, PubMed:17353262, PubMed:18077224). Forms a
CC heterotetramer with IFFO1; the interaction involves LIG4-free XRCC4 and
CC leads to the relocalization of IFFO1 to the sites of DNA damage
CC (PubMed:31548606). Interacts with PNKP; mainly interacts with PNKP when
CC phosphorylated at Thr-233, but is also able to interact at much lower
CC level with PNKP when not unphosphorylated (PubMed:15385968,
CC PubMed:20852255, PubMed:28453785). Interacts with POLL (DNA polymerase
CC lambda) (PubMed:30250067). {ECO:0000269|PubMed:10757784,
CC ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:11080143,
CC ECO:0000269|PubMed:11702069, ECO:0000269|PubMed:12509254,
CC ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:12547193,
CC ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:15385968,
CC ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:17124166,
CC ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:17353262,
CC ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18077224,
CC ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:19332554,
CC ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:20852255,
CC ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435,
CC ECO:0000269|PubMed:21936820, ECO:0000269|PubMed:21982441,
CC ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571,
CC ECO:0000269|PubMed:24984242, ECO:0000269|PubMed:25574025,
CC ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:25934149,
CC ECO:0000269|PubMed:25941166, ECO:0000269|PubMed:26100018,
CC ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:27437582,
CC ECO:0000269|PubMed:28453785, ECO:0000269|PubMed:30250067,
CC ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:33854234,
CC ECO:0000269|PubMed:9242410, ECO:0000269|PubMed:9259561}.
CC -!- SUBUNIT: [Protein XRCC4, C-terminus]: Interacts with XKR4; interacts
CC with the processed form of XKR4, which is cleaved by caspase.
CC {ECO:0000269|PubMed:33725486}.
CC -!- INTERACTION:
CC Q13426; Q8IW19: APLF; NbExp=5; IntAct=EBI-717592, EBI-1256044;
CC Q13426; Q7Z2E3: APTX; NbExp=3; IntAct=EBI-717592, EBI-847814;
CC Q13426; Q2TB18: ASTE1; NbExp=3; IntAct=EBI-717592, EBI-2875586;
CC Q13426; O00499: BIN1; NbExp=4; IntAct=EBI-717592, EBI-719094;
CC Q13426; Q8IZU0: FAM9B; NbExp=7; IntAct=EBI-717592, EBI-10175124;
CC Q13426; O15499: GSC2; NbExp=3; IntAct=EBI-717592, EBI-19954058;
CC Q13426; Q9NVX0: HAUS2; NbExp=3; IntAct=EBI-717592, EBI-720080;
CC Q13426; Q0D2I5: IFFO1; NbExp=5; IntAct=EBI-717592, EBI-742894;
CC Q13426; Q0D2I5-5: IFFO1; NbExp=4; IntAct=EBI-717592, EBI-21251044;
CC Q13426; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-717592, EBI-3044087;
CC Q13426; P49917: LIG4; NbExp=19; IntAct=EBI-717592, EBI-847896;
CC Q13426; P43360: MAGEA6; NbExp=3; IntAct=EBI-717592, EBI-1045155;
CC Q13426; Q9H9Q4: NHEJ1; NbExp=11; IntAct=EBI-717592, EBI-847807;
CC Q13426; Q9H9Q4-1: NHEJ1; NbExp=4; IntAct=EBI-717592, EBI-15891382;
CC Q13426; Q96T60: PNKP; NbExp=9; IntAct=EBI-717592, EBI-1045072;
CC Q13426; Q13426: XRCC4; NbExp=7; IntAct=EBI-717592, EBI-717592;
CC Q13426; Q13426-3: XRCC4; NbExp=3; IntAct=EBI-717592, EBI-12699927;
CC Q13426; P12956: XRCC6; NbExp=3; IntAct=EBI-717592, EBI-353208;
CC Q13426-2; P49917: LIG4; NbExp=11; IntAct=EBI-15891375, EBI-847896;
CC Q13426-2; Q9H9Q4-1: NHEJ1; NbExp=3; IntAct=EBI-15891375, EBI-15891382;
CC Q13426-2; Q13426-2: XRCC4; NbExp=3; IntAct=EBI-15891375, EBI-15891375;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16478998,
CC ECO:0000269|PubMed:21982441, ECO:0000269|PubMed:24984242,
CC ECO:0000269|PubMed:25597996, ECO:0000269|PubMed:25934149,
CC ECO:0000269|PubMed:33725486, ECO:0000269|PubMed:9259561}. Chromosome
CC {ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:27437582,
CC ECO:0000269|PubMed:31548606}. Note=Localizes to site of double-strand
CC breaks. {ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:27437582}.
CC -!- SUBCELLULAR LOCATION: [Protein XRCC4, C-terminus]: Cytoplasm
CC {ECO:0000269|PubMed:33725486}. Note=Translocates from the nucleus to
CC the cytoplasm following cleavage by caspase-3 (CASP3).
CC {ECO:0000269|PubMed:33725486}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q13426-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13426-2; Sequence=VSP_009473;
CC Name=3;
CC IsoId=Q13426-3; Sequence=VSP_009474;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:8548796}.
CC -!- PTM: Phosphorylated by PRKDC at the C-terminus in response to DNA
CC damage; Ser-260 and Ser-320 constitute the main phosphorylation sites
CC (PubMed:9430729, PubMed:15177042, PubMed:14599745, PubMed:12547193,
CC PubMed:26666690, PubMed:28500754, PubMed:30247612). Phosphorylations by
CC PRKDC at the C-terminus of XRCC4 and NHEJ1/XLF are highly redundant and
CC regulate ability of the XRCC4-NHEJ1/XLF subcomplex to bridge DNA
CC (PubMed:22228831, PubMed:28500754). Phosphorylation by PRKDC does not
CC prevent interaction with NHEJ1/XLF but disrupts ability to bridge DNA
CC and promotes detachment from DNA (PubMed:22228831, PubMed:28500754).
CC Phosphorylation at Ser-327 and Ser-328 by PRKDC promotes recognition by
CC the SCF(FBXW7) complex and subsequent ubiquitination via 'Lys-63'-
CC linked ubiquitin (PubMed:26774286). Phosphorylation at Thr-233 by CK2
CC promotes interaction with PNKP; regulating PNKP activity and
CC localization to DNA damage sites (PubMed:15385968, PubMed:20852255,
CC PubMed:28453785). Phosphorylation by CK2 promotes interaction with APTX
CC (PubMed:15380105). {ECO:0000269|PubMed:12547193,
CC ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:15177042,
CC ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:15385968,
CC ECO:0000269|PubMed:20852255, ECO:0000269|PubMed:22228831,
CC ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:26774286,
CC ECO:0000269|PubMed:28453785, ECO:0000269|PubMed:28500754,
CC ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:9430729}.
CC -!- PTM: Ubiquitinated at Lys-296 by the SCF(FBXW7) complex via 'Lys-63'-
CC linked ubiquitination, thereby promoting double-strand break repair:
CC the SCF(FBXW7) complex specifically recognizes XRCC4 when
CC phosphorylated at Ser-327 and Ser-328 by PRKDC, and 'Lys-63'-linked
CC ubiquitination facilitates DNA non-homologous end joining (NHEJ) by
CC enhancing association with XRCC5/Ku80 and XRCC6/Ku70 (PubMed:26774286).
CC Monoubiquitinated (PubMed:16412978). {ECO:0000269|PubMed:16412978,
CC ECO:0000269|PubMed:26774286}.
CC -!- PTM: [DNA repair protein XRCC4]: Undergoes proteolytic processing by
CC caspase-3 (CASP3) (Probable) (PubMed:33725486). This generates the
CC protein XRCC4, C-terminus (XRCC4/C), which translocates to the
CC cytoplasm and activates phospholipid scramblase activity of XKR4,
CC thereby promoting phosphatidylserine exposure on apoptotic cell surface
CC (PubMed:33725486). {ECO:0000269|PubMed:33725486,
CC ECO:0000305|PubMed:10922471}.
CC -!- DISEASE: Short stature, microcephaly, and endocrine dysfunction (SSMED)
CC [MIM:616541]: A disease characterized by short stature and microcephaly
CC apparent at birth, progressive postnatal growth failure, and endocrine
CC dysfunction. In affected adults endocrine features include
CC hypergonadotropic hypogonadism, multinodular goiter, and diabetes
CC mellitus. Variable features observed in some patients are progressive
CC ataxia, and lymphopenia or borderline leukopenia.
CC {ECO:0000269|PubMed:24389050, ECO:0000269|PubMed:25728776,
CC ECO:0000269|PubMed:25742519, ECO:0000269|PubMed:25839420,
CC ECO:0000269|PubMed:25872942, ECO:0000269|PubMed:26255102,
CC ECO:0000269|PubMed:32524007}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the XRCC4-XLF family. XRCC4 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Sumoylation at Lys-210 was initially reported to regulate
CC nuclear localization and recombination efficiency of XRCC4
CC (PubMed:16478998). This result is however not confirmed by another
CC study (PubMed:25934149). {ECO:0000269|PubMed:16478998,
CC ECO:0000269|PubMed:25934149}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/xrcc4/";
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DR EMBL; U40622; AAC50339.1; -; mRNA.
DR EMBL; AF055285; AAD47297.1; -; Genomic_DNA.
DR EMBL; AF055279; AAD47297.1; JOINED; Genomic_DNA.
DR EMBL; AF055280; AAD47297.1; JOINED; Genomic_DNA.
DR EMBL; AF055281; AAD47297.1; JOINED; Genomic_DNA.
DR EMBL; AF055282; AAD47297.1; JOINED; Genomic_DNA.
DR EMBL; AF055283; AAD47297.1; JOINED; Genomic_DNA.
DR EMBL; AF055284; AAD47297.1; JOINED; Genomic_DNA.
DR EMBL; AF055285; AAD47298.1; -; Genomic_DNA.
DR EMBL; AF055279; AAD47298.1; JOINED; Genomic_DNA.
DR EMBL; AF055280; AAD47298.1; JOINED; Genomic_DNA.
DR EMBL; AF055281; AAD47298.1; JOINED; Genomic_DNA.
DR EMBL; AF055282; AAD47298.1; JOINED; Genomic_DNA.
DR EMBL; AF055283; AAD47298.1; JOINED; Genomic_DNA.
DR EMBL; AF055284; AAD47298.1; JOINED; Genomic_DNA.
DR EMBL; AB017445; BAB20668.1; -; mRNA.
DR EMBL; BT007216; AAP35880.1; -; mRNA.
DR EMBL; AK290739; BAF83428.1; -; mRNA.
DR EMBL; AY940097; AAX14046.1; -; Genomic_DNA.
DR EMBL; CH471084; EAW95898.1; -; Genomic_DNA.
DR EMBL; BC005259; AAH05259.1; -; mRNA.
DR EMBL; BC016314; AAH16314.1; -; mRNA.
DR CCDS; CCDS4058.1; -. [Q13426-2]
DR CCDS; CCDS4059.1; -. [Q13426-1]
DR RefSeq; NP_001304941.1; NM_001318012.1. [Q13426-1]
DR RefSeq; NP_001304942.1; NM_001318013.1. [Q13426-3]
DR RefSeq; NP_003392.1; NM_003401.4. [Q13426-2]
DR RefSeq; NP_071801.1; NM_022406.3. [Q13426-1]
DR RefSeq; NP_072044.1; NM_022550.3. [Q13426-2]
DR RefSeq; XP_011541928.1; XM_011543626.1. [Q13426-1]
DR PDB; 1FU1; X-ray; 2.70 A; A/B=1-203.
DR PDB; 1IK9; X-ray; 2.30 A; A/B=1-213.
DR PDB; 3II6; X-ray; 2.40 A; A/B/C/D=1-203.
DR PDB; 3MUD; X-ray; 2.20 A; A/B=2-133.
DR PDB; 3Q4F; X-ray; 5.50 A; C/D/G/H=1-157.
DR PDB; 3RWR; X-ray; 3.94 A; A/B/F/G/J/K/N/P/R/U/V/Y=1-157.
DR PDB; 3SR2; X-ray; 3.97 A; A/B/E/F=1-140.
DR PDB; 3W03; X-ray; 8.49 A; C/D=1-164.
DR PDB; 4XA4; X-ray; 2.33 A; A/B=2-147.
DR PDB; 5CHX; X-ray; 2.30 A; A/B=2-143.
DR PDB; 5CJ0; X-ray; 2.30 A; A/B=2-142.
DR PDB; 5CJ4; X-ray; 3.10 A; A/B/C/D=2-144.
DR PDB; 5E50; X-ray; 1.38 A; C/D=229-236.
DR PDB; 5WJ7; X-ray; 2.50 A; A/B=2-132.
DR PDB; 5WLZ; X-ray; 3.50 A; A/B/C/D=2-132.
DR PDB; 6ABO; X-ray; 2.65 A; A=1-213.
DR PDB; 7LSY; EM; 8.40 A; F/G/O/P=1-336.
DR PDB; 7LT3; EM; 4.60 A; F/G/O/P=1-336.
DR PDB; 7M3P; X-ray; 2.00 A; A/B=2-132.
DR PDB; 7NFC; EM; 4.14 A; K/L/N/O=1-336.
DR PDB; 7NFE; EM; 4.29 A; H/I=1-336.
DR PDBsum; 1FU1; -.
DR PDBsum; 1IK9; -.
DR PDBsum; 3II6; -.
DR PDBsum; 3MUD; -.
DR PDBsum; 3Q4F; -.
DR PDBsum; 3RWR; -.
DR PDBsum; 3SR2; -.
DR PDBsum; 3W03; -.
DR PDBsum; 4XA4; -.
DR PDBsum; 5CHX; -.
DR PDBsum; 5CJ0; -.
DR PDBsum; 5CJ4; -.
DR PDBsum; 5E50; -.
DR PDBsum; 5WJ7; -.
DR PDBsum; 5WLZ; -.
DR PDBsum; 6ABO; -.
DR PDBsum; 7LSY; -.
DR PDBsum; 7LT3; -.
DR PDBsum; 7M3P; -.
DR PDBsum; 7NFC; -.
DR PDBsum; 7NFE; -.
DR AlphaFoldDB; Q13426; -.
DR SMR; Q13426; -.
DR BioGRID; 113352; 78.
DR CORUM; Q13426; -.
DR DIP; DIP-37957N; -.
DR ELM; Q13426; -.
DR IntAct; Q13426; 36.
DR MINT; Q13426; -.
DR STRING; 9606.ENSP00000421491; -.
DR ChEMBL; CHEMBL4296097; -.
DR DrugBank; DB03963; S-(Dimethylarsenic)Cysteine.
DR iPTMnet; Q13426; -.
DR MetOSite; Q13426; -.
DR PhosphoSitePlus; Q13426; -.
DR BioMuta; XRCC4; -.
DR DMDM; 44888352; -.
DR EPD; Q13426; -.
DR jPOST; Q13426; -.
DR MassIVE; Q13426; -.
DR MaxQB; Q13426; -.
DR PaxDb; Q13426; -.
DR PeptideAtlas; Q13426; -.
DR PRIDE; Q13426; -.
DR ProteomicsDB; 59412; -. [Q13426-1]
DR ProteomicsDB; 59413; -. [Q13426-2]
DR ProteomicsDB; 59414; -. [Q13426-3]
DR Antibodypedia; 1873; 464 antibodies from 34 providers.
DR DNASU; 7518; -.
DR Ensembl; ENST00000282268.7; ENSP00000282268.3; ENSG00000152422.16. [Q13426-2]
DR Ensembl; ENST00000338635.10; ENSP00000342011.6; ENSG00000152422.16. [Q13426-1]
DR Ensembl; ENST00000396027.9; ENSP00000379344.4; ENSG00000152422.16. [Q13426-2]
DR Ensembl; ENST00000511817.1; ENSP00000421491.1; ENSG00000152422.16. [Q13426-1]
DR GeneID; 7518; -.
DR KEGG; hsa:7518; -.
DR MANE-Select; ENST00000396027.9; ENSP00000379344.4; NM_003401.5; NP_003392.1. [Q13426-2]
DR UCSC; uc003kib.4; human. [Q13426-1]
DR CTD; 7518; -.
DR DisGeNET; 7518; -.
DR GeneCards; XRCC4; -.
DR HGNC; HGNC:12831; XRCC4.
DR HPA; ENSG00000152422; Low tissue specificity.
DR MalaCards; XRCC4; -.
DR MIM; 194363; gene.
DR MIM; 616541; phenotype.
DR neXtProt; NX_Q13426; -.
DR OpenTargets; ENSG00000152422; -.
DR Orphanet; 99812; LIG4 syndrome.
DR Orphanet; 436182; Microcephalic primordial dwarfism-insulin resistance syndrome.
DR PharmGKB; PA37423; -.
DR VEuPathDB; HostDB:ENSG00000152422; -.
DR eggNOG; ENOG502QWJA; Eukaryota.
DR GeneTree; ENSGT00390000017079; -.
DR HOGENOM; CLU_072334_0_0_1; -.
DR InParanoid; Q13426; -.
DR OMA; MQKDISF; -.
DR PhylomeDB; Q13426; -.
DR TreeFam; TF101204; -.
DR PathwayCommons; Q13426; -.
DR Reactome; R-HSA-164843; 2-LTR circle formation.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR SignaLink; Q13426; -.
DR SIGNOR; Q13426; -.
DR BioGRID-ORCS; 7518; 86 hits in 1083 CRISPR screens.
DR ChiTaRS; XRCC4; human.
DR EvolutionaryTrace; Q13426; -.
DR GeneWiki; XRCC4; -.
DR GenomeRNAi; 7518; -.
DR Pharos; Q13426; Tbio.
DR PRO; PR:Q13426; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q13426; protein.
DR Bgee; ENSG00000152422; Expressed in monocyte and 154 other tissues.
DR ExpressionAtlas; Q13426; baseline and differential.
DR Genevisible; Q13426; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0032807; C:DNA ligase IV complex; IDA:UniProtKB.
DR GO; GO:0005958; C:DNA-dependent protein kinase-DNA ligase 4 complex; IDA:MGI.
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:0070975; F:FHA domain binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0051103; P:DNA ligation involved in DNA repair; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break 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; IBA:GO_Central.
DR GO; GO:0051351; P:positive regulation of ligase activity; IDA:UniProtKB.
DR GO; GO:1905782; P:positive regulation of phosphatidylserine exposure on apoptotic cell surface; IDA:UniProtKB.
DR GO; GO:1990166; P:protein localization to site of double-strand break; IDA:UniProtKB.
DR GO; GO:0010165; P:response to X-ray; IDA:UniProtKB.
DR DisProt; DP00152; -.
DR Gene3D; 1.20.5.370; -; 1.
DR Gene3D; 2.170.210.10; -; 1.
DR InterPro; IPR010585; DNA_repair_prot_XRCC4.
DR InterPro; IPR014751; XRCC4-like_C.
DR InterPro; IPR038051; XRCC4-like_N_sf.
DR InterPro; IPR009089; XRCC4_N_sf.
DR PANTHER; PTHR28559; PTHR28559; 1.
DR Pfam; PF06632; XRCC4; 1.
DR SUPFAM; SSF50809; SSF50809; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Coiled coil; Cytoplasm;
KW Disease variant; DNA damage; DNA recombination; DNA repair; DNA-binding;
KW Dwarfism; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..336
FT /note="DNA repair protein XRCC4"
FT /id="PRO_0000066047"
FT CHAIN 266..336
FT /note="Protein XRCC4, C-terminus"
FT /evidence="ECO:0000305|PubMed:33725486"
FT /id="PRO_0000453296"
FT REGION 1..213
FT /note="Interaction with IFFO1"
FT /evidence="ECO:0000269|PubMed:31548606"
FT REGION 180..213
FT /note="Interaction with LIG4"
FT /evidence="ECO:0000269|PubMed:11702069"
FT REGION 212..249
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 131..165
FT /evidence="ECO:0000255"
FT COILED 184..212
FT /evidence="ECO:0000255"
FT MOTIF 270..275
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:25934149,
FT ECO:0000269|PubMed:33725486"
FT COMPBIAS 295..318
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 265..266
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000305|PubMed:33725486"
FT MOD_RES 53
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745"
FT MOD_RES 193
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MOD_RES 229
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28453785"
FT MOD_RES 233
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000269|PubMed:15385968,
FT ECO:0000269|PubMed:20852255, ECO:0000269|PubMed:28453785,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 260
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:22228831,
FT ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:30247612,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 303
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:22228831"
FT MOD_RES 304
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:28500754,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 315
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MOD_RES 320
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:22228831,
FT ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28500754,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 323
FT /note="Phosphothreonine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"
FT MOD_RES 327
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:26774286,
FT ECO:0000269|PubMed:28500754, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 328
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:26774286,
FT ECO:0000269|PubMed:28500754, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT CROSSLNK 210
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:16478998"
FT CROSSLNK 296
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26774286"
FT VAR_SEQ 298..336
FT /note="NSRPDSSLPETSKKEHISAENMSLETLRNSSPEDLFDEI -> KGRKKETSE
FT KEAV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_009474"
FT VAR_SEQ 298..300
FT /note="NSR -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8548796"
FT /id="VSP_009473"
FT VARIANT 12
FT /note="S -> C (in dbSNP:rs28383138)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_022310"
FT VARIANT 43
FT /note="W -> R (in SSMED; impairs the protein function in
FT DNA double-strand break repair; dbSNP:rs587779351)"
FT /evidence="ECO:0000269|PubMed:24389050,
FT ECO:0000269|PubMed:25728776, ECO:0000269|PubMed:26255102"
FT /id="VAR_075822"
FT VARIANT 56
FT /note="A -> T (in dbSNP:rs28383151)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_022311"
FT VARIANT 82
FT /note="D -> E (in SSMED; impaired ability to repair DNA
FT double-strand breaks)"
FT /evidence="ECO:0000269|PubMed:25742519"
FT /id="VAR_084965"
FT VARIANT 134
FT /note="I -> T (in dbSNP:rs28360135)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_022312"
FT VARIANT 142
FT /note="E -> Q (in dbSNP:rs28360136)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_022313"
FT VARIANT 161..336
FT /note="Missing (in SSMED)"
FT /evidence="ECO:0000269|PubMed:25728776"
FT /id="VAR_084966"
FT VARIANT 161
FT /note="R -> Q (in SSMED; no expression of the protein is
FT observed; complete loss of function in DNA double-strand
FT break repair; dbSNP:rs797045017)"
FT /evidence="ECO:0000269|PubMed:25839420"
FT /id="VAR_075823"
FT VARIANT 210..336
FT /note="Missing (in SSMED)"
FT /evidence="ECO:0000269|PubMed:32524007"
FT /id="VAR_084967"
FT VARIANT 225..336
FT /note="Missing (in SSMED)"
FT /evidence="ECO:0000269|PubMed:25728776,
FT ECO:0000269|PubMed:25872942, ECO:0000269|PubMed:26255102"
FT /id="VAR_084968"
FT VARIANT 240
FT /note="Q -> P (in dbSNP:rs2974446)"
FT /id="VAR_017810"
FT VARIANT 247
FT /note="A -> S (in dbSNP:rs3734091)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_017811"
FT VARIANT 275..336
FT /note="Missing (in SSMED)"
FT /evidence="ECO:0000269|PubMed:25728776,
FT ECO:0000269|PubMed:25839420"
FT /id="VAR_084969"
FT MUTAGEN 4
FT /note="K->E: Abolished interaction with NHEJ1/XLF; when
FT associated with E-99."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 26
FT /note="K->E: Abolished interaction with NHEJ1/XLF; when
FT associated with E-99."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 55
FT /note="E->R: Abolished interaction with NHEJ1/XLF."
FT /evidence="ECO:0000269|PubMed:21768349"
FT MUTAGEN 58
FT /note="D->R: Abolished interaction with NHEJ1/XLF."
FT /evidence="ECO:0000269|PubMed:21768349"
FT MUTAGEN 61
FT /note="M->R: Abolished interaction with NHEJ1/XLF."
FT /evidence="ECO:0000269|PubMed:21768349"
FT MUTAGEN 62
FT /note="E->R: Does not affect interaction with NHEJ1/XLF."
FT /evidence="ECO:0000269|PubMed:21768349"
FT MUTAGEN 65
FT /note="K->E: Strongly decreased interaction with NHEJ1/XLF.
FT Abolished interaction with NHEJ1/XLF; when associated with
FT E-99. Abolished ability to bridge DNA; when associated with
FT E-99. Abolished interaction with NHEJ1/XLF; when associated
FT with E-102."
FT /evidence="ECO:0000269|PubMed:18158905,
FT ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:22287571"
FT MUTAGEN 69
FT /note="E->R: Does not affect interaction with NHEJ1/XLF."
FT /evidence="ECO:0000269|PubMed:21768349"
FT MUTAGEN 71
FT /note="R->E: Abolished interaction with NHEJ1/XLF; when
FT associated with E-99."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 72
FT /note="K->E: Abolished interaction with NHEJ1/XLF; when
FT associated with E-99. Abolished ability to bridge DNA; when
FT associated with E-90 and E-99."
FT /evidence="ECO:0000269|PubMed:18158905,
FT ECO:0000269|PubMed:22287571"
FT MUTAGEN 90
FT /note="K->E: Abolished ability to bridge DNA; when
FT associated with E-72 and E-99."
FT /evidence="ECO:0000269|PubMed:22287571"
FT MUTAGEN 99
FT /note="K->E: Abolished interaction with NHEJ1/XLF; when
FT associated with E-4 or E-26 or E-65 or E-71 or E-72.
FT Abolished ability to bridge DNA; when associated with E-65.
FT Abolished ability to bridge DNA; when associated with E-72
FT and E-90."
FT /evidence="ECO:0000269|PubMed:18158905,
FT ECO:0000269|PubMed:22287571"
FT MUTAGEN 102
FT /note="K->E: Abolished interaction with NHEJ1/XLF; when
FT associated with E-65."
FT /evidence="ECO:0000269|PubMed:18158905"
FT MUTAGEN 106
FT /note="F->E: Abolished interaction with NHEJ1/XLF."
FT /evidence="ECO:0000269|PubMed:21768349"
FT MUTAGEN 140
FT /note="K->R: No change in sumoylation."
FT /evidence="ECO:0000269|PubMed:16478998"
FT MUTAGEN 170
FT /note="E->A: Abolished DNA-binding."
FT /evidence="ECO:0000269|PubMed:22287571"
FT MUTAGEN 192
FT /note="R->A: Abolished DNA-binding."
FT /evidence="ECO:0000269|PubMed:22287571"
FT MUTAGEN 193
FT /note="S->A: In XRCC4-Ala mutant; abolished phosphorylation
FT by PRKDC; does not affect ability to bridge DNA when
FT associated with NHEJ1/XLF phosphorylation-defective mutant;
FT when associated with A-260, A-304, A-315, A-320, A-323, A-
FT 327 and A-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 193
FT /note="S->D: In XRCC4-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with
FT NHEJ1/XLF phospho-mimetic mutant; when associated with D-
FT 260, D-304, D-315, D-320, D-323, D-327 and D-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 210
FT /note="K->R: Abolishes sumoylation. 5-fold decrease in
FT recombination efficiency. Does not affect nuclear
FT localization of XRCC4 and LIG4."
FT /evidence="ECO:0000269|PubMed:16478998,
FT ECO:0000269|PubMed:25934149"
FT MUTAGEN 233
FT /note="T->A: Abolished phosphorylation by CK2, leading to
FT strongly reduced interaction with PNKP."
FT /evidence="ECO:0000269|PubMed:15385968"
FT MUTAGEN 235
FT /note="E->F: Impaired ability mediate double-strand break
FT repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 260
FT /note="S->A: Reduced phosphorylation by PRKDC. In XRCC4-Ala
FT mutant; abolished phosphorylation by PRKDC; does not affect
FT ability to bridge DNA when associated with NHEJ1/XLF
FT phosphorylation-defective mutant; when associated with A-
FT 193, A-304, A-315, A-320, A-323, A-327 and A-328."
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:30247612"
FT MUTAGEN 260
FT /note="S->D: In XRCC4-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with
FT NHEJ1/XLF phospho-mimetic mutant; when associated with D-
FT 193, D-304, D-315, D-320, D-323, D-327 and D-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 262..265
FT /note="DVTD->AVTA: In 2DA; abolished cleavage by caspase
FT and ability to regulate phospholipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:33725486"
FT MUTAGEN 264
FT /note="T->A: Does not affect phosphorylation by CK2."
FT /evidence="ECO:0000269|PubMed:15385968"
FT MUTAGEN 266
FT /note="I->G: Abolished cleavage by caspase and ability to
FT regulate phospholipid scramblase activity."
FT /evidence="ECO:0000269|PubMed:33725486"
FT MUTAGEN 270
FT /note="R->A: Impaired ability to localize in the nucleus."
FT /evidence="ECO:0000269|PubMed:33725486"
FT MUTAGEN 271
FT /note="K->A: Impaired ability to localize in the nucleus,
FT without affecting ability to activate phospholipid
FT scramblase activity of XKR4."
FT /evidence="ECO:0000269|PubMed:33725486"
FT MUTAGEN 271
FT /note="K->R: Abolished nuclear localization of XRCC4 and
FT LIG4. Impaired ability to repair DNA double-strand breaks
FT (DSBs). Reduced ubiquitination by the SCF(FBXW7) complex
FT caused by impaired localization to the nucleus."
FT /evidence="ECO:0000269|PubMed:25934149,
FT ECO:0000269|PubMed:26774286"
FT MUTAGEN 272
FT /note="R->A: Impaired ability to localize in the nucleus,
FT without affecting ability to activate phospholipid
FT scramblase activity of XKR4."
FT /evidence="ECO:0000269|PubMed:33725486"
FT MUTAGEN 273
FT /note="R->A: Impaired ability to localize in the nucleus,
FT without affecting ability to activate phospholipid
FT scramblase activity of XKR4."
FT /evidence="ECO:0000269|PubMed:33725486"
FT MUTAGEN 275
FT /note="R->A: Does not affect ability to localize into the
FT nucleus."
FT /evidence="ECO:0000269|PubMed:33725486"
FT MUTAGEN 282
FT /note="T->A: Does not affect phosphorylation by CK2."
FT /evidence="ECO:0000269|PubMed:15385968"
FT MUTAGEN 285
FT /note="K->R: Does not affect ubiquitination by the
FT SCF(FBXW7) complex."
FT /evidence="ECO:0000269|PubMed:26774286"
FT MUTAGEN 296
FT /note="K->R: Abolished ubiquitination by the SCF(FBXW7)
FT complex."
FT /evidence="ECO:0000269|PubMed:26774286"
FT MUTAGEN 304
FT /note="S->A: In XRCC4-Ala mutant; abolished phosphorylation
FT by PRKDC; does not affect ability to bridge DNA when
FT associated with NHEJ1/XLF phosphorylation-defective mutant;
FT when associated with A-193, A-260, A-315, A-320, A-323, A-
FT 327 and A-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 304
FT /note="S->D: In XRCC4-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with
FT NHEJ1/XLF phospho-mimetic mutant; when associated with D-
FT 193, D-260, D-315, D-320, D-323, D-327 and D-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 308
FT /note="T->A: Does not affect phosphorylation by CK2."
FT /evidence="ECO:0000269|PubMed:15385968"
FT MUTAGEN 308
FT /note="T->R: Does not affect ubiquitination by the
FT SCF(FBXW7) complex."
FT /evidence="ECO:0000269|PubMed:26774286"
FT MUTAGEN 315
FT /note="S->A: In XRCC4-Ala mutant; abolished phosphorylation
FT by PRKDC; does not affect ability to bridge DNA when
FT associated with NHEJ1/XLF phosphorylation-defective mutant;
FT when associated with A-193, A-260, A-304, A-320, A-323, A-
FT 327 and A-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 315
FT /note="S->D: In XRCC4-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with
FT NHEJ1/XLF phospho-mimetic mutant; when associated with D-
FT 193, D-260, D-304, D-320, D-323, D-327 and D-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 320
FT /note="S->A: Slightly reduced phosphorylation by PRKDC. In
FT XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does
FT not affect ability to bridge DNA when associated with
FT NHEJ1/XLF phosphorylation-defective mutant; when associated
FT with A-193, A-260, A-304, A-315, A-323, A-327 and A-328."
FT /evidence="ECO:0000269|PubMed:14599745,
FT ECO:0000269|PubMed:28500754"
FT MUTAGEN 320
FT /note="S->D: In XRCC4-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with
FT NHEJ1/XLF phospho-mimetic mutant; when associated with D-
FT 193, D-260, D-304, D-315, D-323, D-327 and D-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 322
FT /note="E->L: Does not affect ability mediate double-strand
FT break repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 323
FT /note="T->A: In XRCC4-Ala mutant; abolished phosphorylation
FT by PRKDC; does not affect ability to bridge DNA when
FT associated with NHEJ1/XLF phosphorylation-defective mutant;
FT when associated with A-193, A-260, A-304, A-315, A-320, A-
FT 327 and A-328. Does not affect phosphorylation by CK2."
FT /evidence="ECO:0000269|PubMed:15385968,
FT ECO:0000269|PubMed:28500754"
FT MUTAGEN 323
FT /note="T->D: Does not affect ability mediate double-strand
FT break repair. In XRCC4-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with
FT NHEJ1/XLF phospho-mimetic mutant; when associated with D-
FT 193, D-260, D-304, D-315, D-320, D-327 and D-328."
FT /evidence="ECO:0000269|PubMed:25597996,
FT ECO:0000269|PubMed:28500754"
FT MUTAGEN 324
FT /note="L->W: Does not affect ability mediate double-strand
FT break repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 326
FT /note="N->L: Abolished ability mediate double-strand break
FT repair; impaired nuclear localization."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 327..328
FT /note="SS->AA: Reduced ubiquitination by the SCF(FBXW7)
FT complex."
FT /evidence="ECO:0000269|PubMed:26774286"
FT MUTAGEN 327
FT /note="S->A: In XRCC4-Ala mutant; abolished phosphorylation
FT by PRKDC; does not affect ability to bridge DNA when
FT associated with NHEJ1/XLF phosphorylation-defective mutant;
FT when associated with A-193, A-260, A-304, A-315, A-320, A-
FT 323 and A-328."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 327
FT /note="S->D: Does not affect ability mediate double-strand
FT break repair. In XRCC4-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with
FT NHEJ1/XLF phospho-mimetic mutant; when associated with D-
FT 193, D-260, D-304, D-315, D-320, D-323 and D-328."
FT /evidence="ECO:0000269|PubMed:25597996,
FT ECO:0000269|PubMed:28500754"
FT MUTAGEN 328
FT /note="S->A: In XRCC4-Ala mutant; abolished phosphorylation
FT by PRKDC; does not affect ability to bridge DNA when
FT associated with NHEJ1/XLF phosphorylation-defective mutant;
FT when associated with A-193, A-260, A-304, A-315, A-320, A-
FT 323 and A-327."
FT /evidence="ECO:0000269|PubMed:28500754"
FT MUTAGEN 328
FT /note="S->D: Does not affect ability mediate double-strand
FT break repair. In XRCC4-Asp mutant; phospho-mimetic mutant;
FT abolished ability to bridge DNA when associated with
FT NHEJ1/XLF phospho-mimetic mutant; when associated with D-
FT 193, D-260, D-304, D-315, D-320, D-323 and D-327."
FT /evidence="ECO:0000269|PubMed:25597996,
FT ECO:0000269|PubMed:28500754"
FT MUTAGEN 329
FT /note="P->W: Does not affect ability mediate double-strand
FT break repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 330
FT /note="E->L: Does not affect ability mediate double-strand
FT break repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 331
FT /note="D->L: Does not affect ability mediate double-strand
FT break repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 332
FT /note="L->W: Does not affect ability mediate double-strand
FT break repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 333
FT /note="F->Y: Does not affect ability mediate double-strand
FT break repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT MUTAGEN 334
FT /note="D->L: Does not affect ability mediate double-strand
FT break repair."
FT /evidence="ECO:0000269|PubMed:25597996"
FT STRAND 2..10
FT /evidence="ECO:0007829|PDB:7M3P"
FT STRAND 13..26
FT /evidence="ECO:0007829|PDB:7M3P"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:7M3P"
FT STRAND 31..37
FT /evidence="ECO:0007829|PDB:7M3P"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:7M3P"
FT HELIX 49..58
FT /evidence="ECO:0007829|PDB:7M3P"
FT HELIX 63..74
FT /evidence="ECO:0007829|PDB:7M3P"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:5WJ7"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:7M3P"
FT TURN 90..93
FT /evidence="ECO:0007829|PDB:7M3P"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:7M3P"
FT STRAND 104..112
FT /evidence="ECO:0007829|PDB:7M3P"
FT HELIX 119..132
FT /evidence="ECO:0007829|PDB:7M3P"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:5CJ4"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:1FU1"
FT HELIX 179..201
FT /evidence="ECO:0007829|PDB:1FU1"
SQ SEQUENCE 336 AA; 38287 MW; BE5FB99153479A4E CRC64;
MERKISRIHL VSEPSITHFL QVSWEKTLES GFVITLTDGH SAWTGTVSES EISQEADDMA
MEKGKYVGEL RKALLSGAGP ADVYTFNFSK ESCYFFFEKN LKDVSFRLGS FNLEKVENPA
EVIRELICYC LDTIAENQAK NEHLQKENER LLRDWNDVQG RFEKCVSAKE ALETDLYKRF
ILVLNEKKTK IRSLHNKLLN AAQEREKDIK QEGETAICSE MTADRDPVYD ESTDEESENQ
TDLSGLASAA VSKDDSIISS LDVTDIAPSR KRRQRMQRNL GTEPKMAPQE NQLQEKENSR
PDSSLPETSK KEHISAENMS LETLRNSSPE DLFDEI
