   Expression  |  Overview  |  BIOLOGY  |  Function  |  Maps  |  MOLECULES  |  Transcripts  |  Proteins  |  I
   ntrons  and exons  |  Main Supporting Clones  | Table of all supporting clones | Fasta Sequences |  BIBLIO
   abstracts and RIFs
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   Homo sapiens gene XRCC4 encoding X-ray repair complementing defective repair in Chinese hamster cells 4.
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   Overview back to top
   [RefSeq  Summary]  The  protein  encoded  by  this  gene  functions  together  with  DNA ligase IV and the
   DNA-dependent  protein  kinase  in the repair of DNA double-strand break by non-homologous end joining and
   the  completion of V(D)J recombination events. The non-homologous end-joining pathway is required both for
   normal  development and for suppression of tumors. This gene functionally complements XR-1 Chinese hamster
   ovary  cell  mutant,  which  is  impaired  in  DNA double-strand breaks produced by ionizing radiation and
   restriction  enzymes. This gene contains 8 exons, and alternative transcription initiation and alternative
   splicing generates several transcript variants.
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   This  gene  XRCC4,  also  known  as  5_82722901, maps on chromosome 5, at 5q13-q14 according to RefSeq. It
   encodes a x-ray repair complementing 4 defective in Chinese hamster family member. From LocusLink Proteome
   or GOA annotation, the products would be involved in double-strand break repair, DNA recombination.
   Expression back to top
   According  to  acembly, it is expressed at high level. Its sequence is supported by 114 sequences from 107
   cDNA  clones and produces, by alternative splicing, 11 different transcripts a, b, c, d, e, f, g, h, j, k,
   l  altogether  encoding 9 different protein isoforms. There are 6 probable alternative promotors and 4 non
   overlapping  alternative  last  exons.  The  transcripts appear to differ by truncation of the N-terminus,
   truncation of the C-terminus, presence or absence of a cassette exon.
   Its regulation may use coregulation with neighbour gene, organized in an operon like structure.
   To summarize, the phenotype and function of this gene are:

   Type                                   
   Function     double-strand break repair LocusLink
                DNA recombination         
   Localisation nucleus                    Psort

   BIOLOGY back to top
   Function back to top
   Protein  properties:  DNA  repair  protein  XRCC4 X-ray repair, complementing defective, repair in Chinese
   hamster.
   Maps back to top
   This gene XRCC4 covers 310872 bp, from 82412030 to 82722901 (33), on the direct strand of chromosome 5.
   MOLECULES back to top
   Transcripts back to top
   According to our analysis, this gene produces, by alternative splicing, 11 types of transcripts, predicted
   to  encode  9 distinct proteins. It contains 19 confirmed introns, 18 of which are alternative. Comparison
   to  the  genome  sequence  shows  that  16 introns follow the consensual [gt-ag] rule, 1 the less frequent
   consensus  [gc-ag],  1 is atypical with good support [at-aa] (provided there is no error in the genome), 1
   is fuzzy or ill defined.

   Transcript
   size      5' UTR      3' UTR       # exons Transcr.unit
   variant a
   1609bp    74bp        524bp, polyA 8       276168bp
   variant b
   1655bp    128bp       516bp, polyA 8       276261bp
   variant c
   1696bp    175bp       516bp, polyA 8       276261bp
   variant d
   1657bp    128bp       524bp, polyA 8       276269bp
   variant e
   1247bp    69bp        245bp, polyA 8       233517bp
   variant f
   1231bp    201bp       214bp, polyA 7       215001bp
   variant g
   897bp     no evidence 105bp, polyA 6       170542bp
   variant h
   978bp     197bp       214bp, polyA 5       123786bp
   variant j
   869bp     65bp        459bp        3       34132bp
   variant k
   562bp     107bp       188bp        4       183837bp
   variant l
   941bp     174bp       563bp, polyA 3       147507bp

   mRNA variant Overview (for structural details see previous table)
   a This complete CDS mRNA is 1609 bp long. Its sequence exactly matches the genome. The premessenger has 8
   exons. It covers 276.17 kb on the 33 genome. The protein (336 aa, 38.3 kDa, pI 4.9) contains no Pfam
   motif. It contains 2 coil coil stretch [Psort2]. Taxblast (threshold 10^-3) tracks ancestors down to
   eukaryota.
   b  This complete CDS mRNA is 1655 bp long. We annotate here the sequence derived from the genome, although
   the  best  path through the available clones differs from it in 5 positions. The premessenger has 8 exons.
   It  covers  276.26  kb on the 33 genome. The protein (336 aa, 38.3 kDa, pI 4.9) contains no Pfam motif. It
   contains 2 coil coil stretch [Psort2]. Taxblast (threshold 10^-3) tracks ancestors down to eukaryota.
   c  This complete CDS mRNA is 1696 bp long. We annotate here the sequence derived from the genome, although
   the  best  path through the available clones differs from it in 4 positions. The premessenger has 8 exons.
   It  covers  276.26  kb on the 33 genome. The protein (334 aa, 38.1 kDa, pI 4.9) contains no Pfam motif. It
   contains 2 coil coil stretch [Psort2]. Taxblast (threshold 10^-3) tracks ancestors down to eukaryota.
   d  This complete CDS mRNA is 1657 bp long. We annotate here the sequence derived from the genome, although
   the  best  path through the available clones differs from it in 5 positions. The premessenger has 8 exons.
   It  covers  276.27  kb on the 33 genome. The protein (334 aa, 38.1 kDa, pI 4.9) contains no Pfam motif. It
   contains 2 coil coil stretch [Psort2]. Taxblast (threshold 10^-3) tracks ancestors down to eukaryota.
   e  This complete CDS mRNA is 1247 bp long. Its sequence exactly matches the genome. The premessenger has 8
   exons.  It  covers  233.52  kb  on  the 33 genome. The protein (310 aa, 35.4 kDa, pI 5.2) contains no Pfam
   motif.  It contains 2 coil coil stretch, an ER membrane domain [Psort2]. Taxblast (threshold 10^-3) tracks
   ancestors down to eutheria.
   f  This complete CDS mRNA is 1231 bp long. Its sequence exactly matches the genome. The premessenger has 7
   exons.  It  covers  215.00  kb  on  the 33 genome. The protein (271 aa, 31.1 kDa, pI 5.4) contains no Pfam
   motif.  It contains 2 coil coil stretch, an ER membrane domain [Psort2]. Taxblast (threshold 10^-3) tracks
   ancestors down to eukaryota.
   g  This mRNA is 897 bp long. We annotate here the sequence derived from the genome, although the best path
   through  the  available  clones  differs  from it in 27 positions. The premessenger has 6 exons. It covers
   170.54 kb on the 33 genome. It may be incomplete at the N terminus. The protein (263 aa, 29.8 kDa, pI 5.0)
   contains no Pfam motif. It contains a N-myristoylation domain, 2 coil coil stretch [Psort2].
   h  This  complete CDS mRNA is 978 bp long. Its sequence exactly matches the genome. The premessenger has 5
   exons.  It  covers  123.79  kb  on  the 33 genome. The protein (188 aa, 22.1 kDa, pI 6.4) contains no Pfam
   motif. It contains 2 coil coil stretch, an ER membrane domain [Psort2]. It is predicted to localise in the
   nucleus [Psort2]. Taxblast (threshold 10^-3) tracks ancestors down to eutheria.
   j  This  complete CDS mRNA is 869 bp long. It exactly matches the genome. The premessenger has 3 exons. It
   covers 34.13 kb on the 33 genome. The protein (114 aa, 12.8 kDa, pI 5.3) contains no Pfam motif.
   k  This  complete CDS mRNA is 562 bp long. It exactly matches the genome. The premessenger has 4 exons. It
   covers  183.84  kb  on  the  33 genome. The protein (88 aa, 9.8 kDa, pI 4.6) contains no Pfam motif. It is
   predicted  to  localise  in  the  nucleus  [Psort2].  Taxblast  (threshold 10^-3) tracks ancestors down to
   eutheria.
   l  This  complete CDS mRNA is 941 bp long. Its sequence exactly matches the genome. The premessenger has 3
   exons. It covers 147.51 kb on the 33 genome. The protein (67 aa, 7.9 kDa, pI 10.5) contains no Pfam motif.
   It  contains  a  2nd  peroximal domain, an ER membrane domain [Psort2]. It is predicted to localise in the
   nucleus [Psort2].

   Proteins back to top

   Protein     Extends from      coord on mRNA minimal set of supporting clones
   a complete
   336aa
               Met to Stop       75 to 1085    BC016314
   b complete=a
   336aa
               Met to Stop       129 to 1139   AL558342
                                               AL580186
   c complete
   334aa
               Met to Stop       176 to 1180   U40622
   d complete=c
   334aa
               Met to Stop       129 to 1133   AL543920
                                               BQ421318
   e complete
   310aa
               Met to Stop       70 to 1002    BC005259
   f complete
   271aa
               Met to Stop       202 to 1017   AA398935
                                               BQ226357
   g
   263aa
               1st codon to Stop 1 to 792      BM465969
   h complete
   188aa
               Met to Stop       198 to 764    AA398935
                                               AA398779
   j complete
   114aa
               Met to Stop       66 to 410     CA453949
   k complete
   88aa
               Met to Stop       108 to 374    IMAGE:3351834
   l complete
   67aa
               Met to Stop       175 to 378    BC010655
                                               BU171074

   Warning:  we  annotate  only one open reading frame (ORF) per mRNA, choosing the longest, and deriving its
   sequence  from the underlying genome. If there is an error in the genome, a better ORF may be derived from
   the  cDNA consensus sequence. It is also possible that the cell uses another frame, or makes more than one
   product  per  mRNA.  The  ORF  we  annotate  on each transcript is shown as a broad solid pink area on the
   drawing.  An  open reading frame that does not cover most of the standard gt-ag or gc-ag intron boundaries
   (both  drawn  in pink, blue being reserved for atypical splice sites) is in our opinion suspicious. If you
   are  interested  in  the  gene, we recommend that you reanalyse yourself all these possibilities using the
   sequences given here, in particular the Acembly reference sequences, which represent the consensus of cDNA
   sequences guided by the genome sequence.
   Intron exon structure and support back to top

                              In
                              variant Length Coord on
                                             gene             Supporting
                                                              clone (s)
   Alternative exon 1         b, d    118    1 to 118         NM_003401
                                                              NM_022406
   Alternative exon 2         c       165    1 to 165         NM_022550
   Alternative exon 3         e       59     60 to 118        BC005259
   Alternative exon 4         j       55     64 to 118        CA453949
   Alternative exon 5                 17     102 to 118       CB144620
   Alternative exon 6         a       64     102 to 165       BC016314
   Alternative intron [gt-ag] b, d, e,
                              j       27294  119 to 27412     NM_003401
                                                              and 24 others
   Alternative intron [gt-ag] a, c    27247  166 to 27412     NM_022550
                                                              and 6 others
   Alternative exon 7         f       191    18576 to 18766   BQ226357
   Alternative intron [gt-ag] f       8646   18767 to 27412   BQ226357
   Exon 8                     a, b, c,
                              d, e, f,
                              j       149    27413 to 27561   NM_003401
                                                              and 32 others
   Intron [gt-ag]             a, b, c,
                              d, e, f,
                              j       5969   27562 to 33530   BI828556
                                                              and 42 others
   Alternative exon 9         a, b, c,
                              d, e, f 176    33531 to 33706   NM_003401
                                                              and 39 others
   Alternative exon 10        j       665    33531 to 34195   CA453949
   Alternative intron [gt-ag] a, b, c,
                              d, e, f 84566  33707 to 118272  BG499117
                                                              and 40 others
   Alternative exon 11        g       96     105309 to 105404 BM465969
   Alternative intron [gt-ag] g       12868  105405 to 118272 BM465969
                                                              BX279574
   Alternative exon 12        h       263    109791 to 110053 AA398779
   Alternative intron [gc-ag] h       8219   110054 to 118272 AA398779
   Exon 13                    a, b, c,
                              d, e, f,
                              g, h    167    118273 to 118439 NM_003401
                                                              and 31 others
   Alternative intron Fuzzy           4514   118440 to 122953 BI464058
   Alternative intron [gt-ag] a, b, c,
                              d, e, f,
                              g, h    7615   118440 to 126054 NM_003401
                                                              and 32 others
   Alternative exon 14                10     122954 to 122963 BI464058
   Alternative intron [at-aa]         3100   122964 to 126063 BI464058
   Alternative exon 15        a, b, c,
                              d, e, f,
                              g, h    156    126055 to 126210 NM_003401
                                                              and 20 others
   Alternative exon 16                147    126064 to 126210
   Alternative intron [gt-ag] a, b, c,
                              d, e, f,
                              g, h    1107   126211 to 127317 NM_003401
                                                              and 23 others
   Alternative exon 17        k       85     127036 to 127120 BE254850
   Alternative intron [gt-ag] k       197    127121 to 127317 BE254850
   Exon 18                    a, b, c,
                              d, e, f,
                              g, h, k 107    127318 to 127424 NM_003401
                                                              and 15 others
   Alternative intron [gt-ag] a, b, c,
                              d, e, g,
                              k       53608  127425 to 181032 NM_003401
                                                              and 16 others
   Alternative intron [gt-ag] f, h    105867 127425 to 233291 BC005259
                                                              and 2 others
   Alternative exon 19        l       159    128755 to 128913 BU171074
   Alternative intron [gt-ag] l       52119  128914 to 181032 BU171074
                                                              and 6 others
   Alternative exon 20        a, b, c,
                              d, e, g,
                              k, l    148    181033 to 181180 NM_003401
                                                              and 19 others
   Alternative intron [gt-ag] e       52111  181181 to 233291 BC005259
                                                              BE748849
   Alternative intron [gt-ag] a, b, g,
                              l       94447  181181 to 275627 AA065267
                                                              and 16 others
   Alternative intron [gt-ag] c, d    94453  181181 to 275633 NM_003401
                                                              and 4 others
   Alternative intron [gt-ag] k       129470 181181 to 310650 BE254850
   Alternative exon 21        e, f, h 285    233292 to 233576 AA398935
   Alternative exon 22        g       223    275628 to 275850 BM465969
   Alternative exon 23        b, l    634    275628 to 276261 AI795996
                                                              and 2 others
   Alternative exon 24        a       642    275628 to 276269 BG199056
   Alternative exon 25        c       628    275634 to 276261 NM_003401
                                                              and 2 others
   Alternative exon 26        d       636    275634 to 276269
   Exon 27                    k       222    310651 to 310872

   A  clone  supports  an exon or an intron if it has exactly the same boundaries. A specified intron, either
   typical  [gt-ag] or [gc-ag] both shown in pink, or atypical and shown in blue on the drawing, has at least
   one  clone  exactly  matching  the  genome  over 8 bp on each side. Some supported exons or introns may be
   shown,  although  the  corresponding  variants  are  not displayed. If an exon is supported by overlapping
   clones,  they  are  not  listed.  This  is  frequently  the  case  for  the last (and first) exon, because
   alternative  polyadenylation is so prevalent that we have chosen to merge and show only the longest 3'UTR.
   All  features  in  the  table  (up  to  programming  bugs)  are supported by mRNAs or ESTs from the public
   databases (DDBJ/EMBL/GenBank).
   Main supporting clones for gene XRCC4 back to top
   The  tables  show  the  alignments  of  the  NCBI reference sequences (NM) then the minimal list of clones
   necessary  to  reconstruct  the  set  of Acembly reference mRNAs (AM). Each AM sequence is a "golden path"
   composite  of  cDNAs, where we choose, for each segment, the clone compatible with the intron structure of
   the variant that best matches the genome The table of all clones is elsewhere.
   .

   Clone     Sequence  match over #bp
                       (% length)     # differences
                                      (% id)          Gene and
                                                      transcript Properties
   NM_003401 NM_003401 1649 bp (100%) 3 err (99.8%id) XRCC4.d    complete CDS
   NM_022406 NM_022406 1655 bp (100%) 4 err (99.8%id) XRCC4.b    complete CDS
   NM_022550 NM_022550 1696 bp (100%) 3 err (99.8%id) XRCC4.c    complete CDS

   Clone Tissue Sequence match over #bp
   (% length) # differences
   (% id) Gene and
   transcript Properties
   AB017445 AB017445 1153 bp (99%) 8 err (99.3%id) XRCC4.a complete CDS
   BC005259 Bone marrow, acute myelogenous leukemia BC005259 1244 bp (100%) 1 err (99.9%id) XRCC4.e complete
   CDS
   BC016314 Bone marrow, acute myelogenous leukemia BC016314 1600 bp (99%) 3 err (99.8%id) XRCC4.a complete
   CDS
   CS0DI063YD15 placenta AL551668 752 bp (100%) no error (100%id) XRCC4.d complete CDS, fully sequenced
   AL575167 776 bp (100%) 23 err (97.0%id) XRCC4.d
   CS0DJ005YD14  T  cells from T cell leukemia AL558342 755 bp (100%) no error (100%id) XRCC4.b complete CDS,
   fully sequenced
   AL580186 811 bp (100%) 5 err (99.4%id) XRCC4.b
   IMAGE:3838919  from  acute myelogenous leukemia bone marrow BE748380 525 bp (100%) 1 err (99.8%id) XRCC4.e
   complete CDS, fully sequenced
   BE748849 656 bp (100%) 9 err (98.6%id) XRCC4.e
   U40622 U40622 1571 bp (100%) 3 err (99.8%id) XRCC4.c complete CDS
   CS0DI005YF13 placenta AL543920 842 bp (93%) 1 err (99.9%id) XRCC4.d complete CDS
   AL570210 562 bp (97%) 18 err (96.9%id) XRCC4.d
   IMAGE:3351834 BE254850 569 bp (93%) no error (100%id) XRCC4.k complete CDS
   IMAGE:3873301 retinoblastoma eye BC010655 892 bp (100%) 9 err (99.0%id) XRCC4.l complete CDS
   BE781955 529 bp (71%) 48 err (93.5%id) XRCC4.l
   IMAGE:3866545 retinoblastoma eye BE778165 762 bp (97%) 19 err (97.6%id) XRCC4.l complete CDS
   IMAGE:3870027 retinoblastoma eye BE781259 792 bp (85%) 24 err (97.4%id) XRCC4.l complete CDS
   IMAGE:3872372 retinoblastoma eye BE780721 732 bp (99%) 18 err (97.6%id) XRCC4.l complete CDS
   IMAGE:3874915 retinoblastoma eye BE783342 721 bp (72%) 51 err (94.9%id) XRCC4.l complete CDS
   IMAGE:5547216 retinoblastoma eye BM564730 821 bp (80%) 18 err (98.2%id) XRCC4.l complete CDS
   IMAGE:6144242 retinoblastoma eye BU171074 921 bp (100%) 21 err (97.7%id) XRCC4.l complete CDS
   IMAGE:6718597 CA453949 869 bp (100%) 9 err (99.0%id) XRCC4.j complete CDS

   .
   BIBLIO abstracts and RIFs back to top
     * J Mol Biol 2003 Feb 7;326(1):93-103. Coordinated assembly of Ku and p460 subunits of the DNA-dependent
       protein  kinase  on  DNA ends is necessary for XRCC4-ligase IV recruitment. Coordinated assembly of Ku
       and  p460  subunits  of  the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV
       recruitment
     * Nat  Struct  Biol  2001 Dec;8(12):1015-9. Crystal structure of an Xrcc4-DNA ligase IV complex. crystal
       structure of an Xrcc4-DNA ligase IV complex
     * Carcinogenesis 2000 Nov;21(11):1977-81. Identification of single nucleotide polymorphisms in human DNA
       repair genes.
     * J  Biol  Chem  2000  Nov 3;275(44):34787-96. DNA ligase IV and XRCC4 form a stable mixed tetramer that
       functions synergistically with other repair factors in a cell-free end-joining system.
     * J  Biol  Chem  2000 Aug 25;275(34):26196-205. Interactions of the DNA ligase IV-XRCC4 complex with DNA
       ends and the DNA-dependent protein kinase.
     * Nature  2000 Apr 20;404(6780):897-900. Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis,
       genomic stability and development.
     * Mol Cell Biol 2000 May;20(9):2996-3003. Ku recruits the XRCC4-ligase IV complex to DNA ends.
     * Genes Cells 1999 Feb;4(2):77-85. The biochemistry and biological significance of nonhomologous DNA end
       joining: an essential repair process in multicellular eukaryotes.
     * Cell 1998 Dec 23;95(7):891-902. A critical role for DNA end-joining proteins in both lymphogenesis and
       neurogenesis.
     * Cell  1995  Dec 29;83(7):1079-89. The XRCC4 gene encodes a novel protein involved in DNA double-strand
       break repair and V(D)J recombination.
     * Genomics 1995 May 1;27(1):211-4. Regional localization of the XRCC4 human radiation repair gene.
     * Am  J  Hum  Genet  1990  Sep;47(3):459-69.  Human  chromosome  5  complements  the  DNA  double-strand
       break-repair deficiency and gamma-ray sensitivity of the XR-1 hamster variant.

   .
   A bientot.
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