DNA repair protein XRCC4

Details

Name
DNA repair protein XRCC4
Kind
protein
Synonyms
  • hXRCC4
  • X-ray repair cross-complementing protein 4
Gene Name
XRCC4
UniProtKB Entry
Q13426Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0003147|DNA repair protein XRCC4
MERKISRIHLVSEPSITHFLQVSWEKTLESGFVITLTDGHSAWTGTVSESEISQEADDMA
MEKGKYVGELRKALLSGAGPADVYTFNFSKESCYFFFEKNLKDVSFRLGSFNLEKVENPA
EVIRELICYCLDTIAENQAKNEHLQKENERLLRDWNDVQGRFEKCVSAKEALETDLYKRF
ILVLNEKKTKIRSLHNKLLNAAQEREKDIKQEGETAICSEMTADRDPVYDESTDEESENQ
TDLSGLASAAVSKDDSIISSLDVTDIAPSRKRRQRMQRNLGTEPKMAPQENQLQEKENSR
PDSSLPETSKKEHISAENMSLETLRNSSPEDLFDEI
Number of residues
336
Molecular Weight
38286.315
Theoretical pI
4.63
GO Classification
Functions
FHA domain binding / identical protein binding
Processes
immunoglobulin V(D)J recombination / protein localization to site of double-strand break
Components
site of double-strand break
General Function
DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:16412978, PubMed:17124166, PubMed:17290226, PubMed:22228831, PubMed:25597996, PubMed:25742519, PubMed:25934149, PubMed:26100018, PubMed:26774286, PubMed:8548796). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs) (PubMed:15385968, PubMed:20852255, PubMed:26774286, PubMed:27437582). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:19837014, PubMed:9242410). XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:22228831, PubMed:9242410). Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10757784, PubMed:10854421). Promotes displacement of PNKP from processed strand break termini (PubMed:20852255, PubMed:28453785)
Specific Function
FHA domain binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0011124|DNA repair protein XRCC4 (XRCC4)
ATGGAGAGAAAAATAAGCAGAATCCACCTTGTTTCTGAACCCAGTATAACTCATTTTCTA
CAAGTATCTTGGGAGAAAACACTGGAATCTGGTTTTGTTATTACACTTACTGATGGTCAT
TCAGCATGGACTGGGACAGTTTCTGAATCAGAGATTTCCCAAGAAGCTGATGACATGGCA
ATGGAAAAAGGGAAATATGTTGGTGAACTGAGAAAAGCATTGTTGTCAGGAGCAGGACCA
GCTGATGTATACACGTTTAATTTTTCTAAAGAGTCTTGTTATTTCTTCTTTGAGAAAAAC
CTGAAAGATGTCTCATTCAGACTTGGTTCCTTCAACCTAGAGAAAGTTGAAAACCCAGCT
GAAGTCATTAGAGAACTTATTTGTTATTGCTTGGACACCATTGCAGAAAATCAAGCCAAA
AATGAGCACCTGCAGAAAGAAAATGAAAGGCTTCTGAGAGATTGGAATGATGTTCAAGGA
CGATTTGAAAAATGTGTGAGTGCTAAGGAAGCTTTGGAGACTGATCTTTATAAGCGGTTT
ATTCTGGTGTTGAATGAGAAGAAAACAAAAATCAGAAGTTTGCATAATAAATTATTAAAT
GCAGCTCAAGAACGAGAAAAGGACATCAAACAAGAAGGGGAAACTGCAATCTGTTCTGAA
ATGACTGCTGACCGAGATCCAGTCTATGATGAGAGTACTGATGAGGAAAGTGAAAACCAA
ACTGATCTCTCTGGGTTGGCTTCAGCTGCTGTAAGTAAAGATGATTCCATTATTTCAAGT
CTTGATGTCACTGATATTGCACCAAGTAGAAAAAGGAGACAGCGAATGCAAAGAAATCTT
GGGACAGAACCTAAAATGGCTCCTCAGGAGAATCAGCTTCAAGAAAAGGAAAAGCCTGAT
TCTTCACTACCTGAGACGTCTAAAAAGGAGCACATCTCAGCTGAAAACATGTCTTTAGAA
ACTCTGAGAAACAGCAGCCCAGAAGACCTCTTTGATGAGATTTAA
Chromosome Location
5
Locus
5q14.2
External Identifiers
ResourceLink
UniProtKB IDQ13426
UniProtKB Entry NameXRCC4_HUMAN
GenBank Protein ID1151115
GenBank Gene IDU40622
GeneCard IDXRCC4
GenAtlas IDXRCC4
HGNC IDHGNC:12831
PDB ID(s)1FU1, 1IK9, 3II6, 3MUD, 3Q4F, 3RWR, 3SR2, 3W03, 4XA4, 5CHX, 5CJ0, 5CJ4, 5E50, 5WJ7, 5WLZ, 6ABO, 7LSY, 7LT3, 7M3P, 7NFC, 7NFE, 8BH3, 8BHV, 8BHY, 8BOT, 8EZA, 8EZB
KEGG IDhsa:7518
NCBI Gene ID7518
General References
  1. Li Z, Otevrel T, Gao Y, Cheng HL, Seed B, Stamato TD, Taccioli GE, Alt FW: The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination. Cell. 1995 Dec 29;83(7):1079-89. [Article]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Critchlow SE, Bowater RP, Jackson SP: Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV. Curr Biol. 1997 Aug 1;7(8):588-98. [Article]
  5. Leber R, Wise TW, Mizuta R, Meek K: The XRCC4 gene product is a target for and interacts with the DNA-dependent protein kinase. J Biol Chem. 1998 Jan 16;273(3):1794-801. [Article]
  6. Lee KJ, Jovanovic M, Udayakumar D, Bladen CL, Dynan WS: Identification of DNA-PKcs phosphorylation sites in XRCC4 and effects of mutations at these sites on DNA end joining in a cell-free system. DNA Repair (Amst). 2004 Mar 4;3(3):267-76. [Article]
  7. Grawunder U, Wilm M, Wu X, Kulesza P, Wilson TE, Mann M, Lieber MR: Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells. Nature. 1997 Jul 31;388(6641):492-5. [Article]
  8. Chen L, Trujillo K, Sung P, Tomkinson AE: Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase. J Biol Chem. 2000 Aug 25;275(34):26196-205. [Article]
  9. Nick McElhinny SA, Snowden CM, McCarville J, Ramsden DA: Ku recruits the XRCC4-ligase IV complex to DNA ends. Mol Cell Biol. 2000 May;20(9):2996-3003. [Article]
  10. Hsu HL, Yannone SM, Chen DJ: Defining interactions between DNA-PK and ligase IV/XRCC4. DNA Repair (Amst). 2002 Mar 28;1(3):225-35. [Article]
  11. Calsou P, Delteil C, Frit P, Drouet J, Salles B: Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment. J Mol Biol. 2003 Feb 7;326(1):93-103. [Article]
  12. Clements PM, Breslin C, Deeks ED, Byrd PJ, Ju L, Bieganowski P, Brenner C, Moreira MC, Taylor AM, Caldecott KW: The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. DNA Repair (Amst). 2004 Nov 2;3(11):1493-502. [Article]
  13. Foster RE, Nnakwe C, Woo L, Frank KM: Monoubiquitination of the nonhomologous end joining protein XRCC4. Biochem Biophys Res Commun. 2006 Mar 3;341(1):175-83. Epub 2006 Jan 6. [Article]
  14. Ahnesorg P, Smith P, Jackson SP: XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell. 2006 Jan 27;124(2):301-13. [Article]
  15. Yurchenko V, Xue Z, Sadofsky MJ: SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair. Mol Cell Biol. 2006 Mar;26(5):1786-94. [Article]
  16. Kanno S, Kuzuoka H, Sasao S, Hong Z, Lan L, Nakajima S, Yasui A: A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses. EMBO J. 2007 Apr 18;26(8):2094-103. Epub 2007 Mar 29. [Article]
  17. Iles N, Rulten S, El-Khamisy SF, Caldecott KW: APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks. Mol Cell Biol. 2007 May;27(10):3793-803. Epub 2007 Mar 12. [Article]
  18. Macrae CJ, McCulloch RD, Ylanko J, Durocher D, Koch CA: APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-dependent hyperphosphorylation following ionizing radiation. DNA Repair (Amst). 2008 Feb 1;7(2):292-302. [Article]
  19. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  20. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  21. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  22. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  23. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  24. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  25. Craxton A, Somers J, Munnur D, Jukes-Jones R, Cain K, Malewicz M: XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair. Cell Death Differ. 2015 Jun;22(6):890-7. doi: 10.1038/cdd.2015.22. Epub 2015 Mar 13. [Article]
  26. Xing M, Yang M, Huo W, Feng F, Wei L, Jiang W, Ning S, Yan Z, Li W, Wang Q, Hou M, Dong C, Guo R, Gao G, Ji J, Zha S, Lan L, Liang H, Xu D: Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway. Nat Commun. 2015 Feb 11;6:6233. doi: 10.1038/ncomms7233. [Article]
  27. Ochi T, Blackford AN, Coates J, Jhujh S, Mehmood S, Tamura N, Travers J, Wu Q, Draviam VM, Robinson CV, Blundell TL, Jackson SP: DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science. 2015 Jan 9;347(6218):185-8. doi: 10.1126/science.1261971. [Article]
  28. Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L: Crystal structure of an Xrcc4-DNA ligase IV complex. Nat Struct Biol. 2001 Dec;8(12):1015-9. [Article]
  29. Modesti M, Junop MS, Ghirlando R, van de Rakt M, Gellert M, Yang W, Kanaar R: Tetramerization and DNA ligase IV interaction of the DNA double-strand break repair protein XRCC4 are mutually exclusive. J Mol Biol. 2003 Nov 21;334(2):215-28. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
S-(Dimethylarsenic)CysteineexperimentalunknowntargetDetails