Homo sapiens L. (human) [HSA]

FULL NAME: X-ray repair cross-complementing protein 5


DESCRIPTION:
Single stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. The XRCC5/6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription.

MISCELLANEOUS:
Individuals with systemic lupus erythematosus (SLE) and related disorders produce extremely large amounts of autoantibodies to XRCC6 and XRCC5.


STRUCTURE SIMILARITY:
Contains 1 Ku domain.
Belongs to the ku80 family.


SUBUNIT STRUCTURE:
Heterodimer of a 70 kDa and a 80 kDa subunit. The dimer associates in a DNA-dependent manner with PRKDC to form the DNA-dependent protein kinase complex DNA-PK, and with the LIG4-XRCC4 complex. The dimer also associates with NAA15, and this complex displays DNA binding activity towards the osteocalcin FGF response element (OCFRE). In addition, the 80 kDa subunit binds to the osteoblast-specific transcription factors MSX2 and RUNX2. Interacts with ELF3. May interact with APLF. The XRCC5/6 dimer associates in a DNA-dependent manner with APEX1.


ENZYME REGULATION:
The EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage.


POST-TRANSLATIONAL MODIFICATION:
Sumoylated.
Phosphorylated on serine residues. Phosphorylation by PRKDC may enhance helicase activity.


PROTEIN TYPE(S):
3'-5' DNA helicase


RELATED PATHWAY(S):
non-homologous end-joining (NHEJ)


RELATED DISEASE(S):
systemic lupus erythematosus (SLE)


Amino acids sequence

        10         20         30         40         50         60
MVRSGNKAAV VLCMDVGFTM SNSIPGIESP FEQAKKVITM FVQRQVFAEN KDEIALVLFG
        70         80         90        100        110        120
TDGTDNPLSG GDQYQNITVH RHLMLPDFDL LEDIESKIQP GSQQADFLDA LIVSMDVIQH
       130        140        150        160        170        180
ETIGKKFEKR HIEIFTDLSS RFSKSQLDII IHSLKKCDIS LQFFLPFSLG KEDGSGDRGD
       190        200        210        220        230        240
GPFRLGGHGP SFPLKGITEQ QKEGLEIVKM VMISLEGEDG LDEIYSFSES LRKLCVFKKI
       250        260        270        280        290        300
ERHSIHWPCR LTIGSNLSIR IAAYKSILQE RVKKTWTVVD AKTLKKEDIQ KETVYCLNDD
       310        320        330        340        350        360
DETEVLKEDI IQGFRYGSDI VPFSKVDEEQ MKYKSEGKCF SVLGFCKSSQ VQRRFFMGNQ
       370        380        390        400        410        420
VLKVFAARDD EAAAVALSSL IHALDDLDMV AIVRYAYDKR ANPQVGVAFP HIKHNYECLV
       430        440        450        460        470        480
YVQLPFMEDL RQYMFSSLKN SKKYAPTEAQ LNAVDALIDS MSLAKKDEKT DTLEDLFPTT
       490        500        510        520        530        540
KIPNPRFQRL FQCLLHRALH PREPLPPIQQ HIWNMLNPPA EVTTKSQIPL SKIKTLFPLI
       550        560        570        580        590        600
EAKKKDQVTA QEIFQDNHED GPTAKKLKTE QGGAHFSVSS LAEGSVTSVG SVNPAENFRV
       610        620        630        640        650        660
LVKQKKASFE EASNQLINHI EQFLDTNETP YFMKSIDCIR AFREEAIKFS EEQRFNNFLK
       670        680        690        700        710        720
ALQEKVEIKQ LNHFWEIVVQ DGITLITKEE ASGSSVTAEE AKKFLAPKDK PSGDTAAVFE
       730
EGGDVDDLLD MI    

Encoded by XRCC5 gene

FULL NAME: X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)


OTHER NAME(S):
FLJ39089
KARP-1
KARP1
KU80
KUB2
Ku86
NFIV


DESCRIPTION:
The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atggtgcggt cggggaataa ggcagctgtt gtgctgtgta tggacgtggg ctttaccatg
        70         80         90        100        110        120
agtaactcca ttcctggtat agaatcccca tttgaacaag caaagaaggt gataaccatg
       130        140        150        160        170        180
tttgtacagc gacaggtgtt tgctgagaac aaggatgaga ttgctttagt cctgtttggt
       190        200        210        220        230        240
acagatggca ctgacaatcc cctttctggt ggggatcagt atcagaacat cacagtgcac
       250        260        270        280        290        300
agacatctga tgctaccaga ttttgatttg ctggaggaca ttgaaagcaa aatccaacca
       310        320        330        340        350        360
ggttctcaac aggctgactt cctggatgca ctaatcgtga gcatggatgt gattcaacat
       370        380        390        400        410        420
gaaacaatag gaaagaagtt tgagaagagg catattgaaa tattcactga cctcagcagc
       430        440        450        460        470        480
cgattcagca aaagtcagct ggatattata attcatagct tgaagaaatg tgacatctcc
       490        500        510        520        530        540
ctgcaattct tcttgccttt ctcacttggc aaggaagatg gaagtgggga cagaggagat
       550        560        570        580        590        600
ggcccctttc gcttaggtgg ccatgggcct tcctttccac taaaaggaat taccgaacag
       610        620        630        640        650        660
caaaaagaag gtcttgagat agtgaaaatg gtgatgatat ctttagaagg tgaagatggg
       670        680        690        700        710        720
ttggatgaaa tttattcatt cagtgagagt ctgagaaaac tgtgcgtctt caagaaaatt
       730        740        750        760        770        780
gagaggcatt ccattcactg gccctgccga ctgaccattg gctccaattt gtctataagg
       790        800        810        820        830        840
attgcagcct ataaatcgat tctacaggag agagttaaaa agacttggac agttgtggat
       850        860        870        880        890        900
gcaaaaaccc taaaaaaaga agatatacaa aaagaaacag tttattgctt aaatgatgat
       910        920        930        940        950        960
gatgaaactg aagttttaaa agaggatatt attcaagggt tccgctatgg aagtgatata
       970        980        990       1000       1010       1020
gttcctttct ctaaagtgga tgaggaacaa atgaaatata aatcggaggg gaagtgcttc
      1030       1040       1050       1060       1070       1080
tctgttttgg gattttgtaa atcttctcag gttcagagaa gattcttcat gggaaatcaa
      1090       1100       1110       1120       1130       1140
gttctaaagg tctttgcagc aagagatgat gaggcagctg cagttgcact ttcctccctg
      1150       1160       1170       1180       1190       1200
attcatgctt tggatgactt agacatggtg gccatagttc gatatgctta tgacaaaaga
      1210       1220       1230       1240       1250       1260
gctaatcctc aagtcggcgt ggcttttcct catatcaagc ataactatga gtgtttagtg
      1270       1280       1290       1300       1310       1320
tatgtgcagc tgcctttcat ggaagacttg cggcaataca tgttttcatc cttgaaaaac
      1330       1340       1350       1360       1370       1380
agtaagaaat atgctcccac cgaggcacag ttgaatgctg ttgatgcttt gattgactcc
      1390       1400       1410       1420       1430       1440
atgagcttgg caaagaaaga tgagaagaca gacacccttg aagacttgtt tccaaccacc
      1450       1460       1470       1480       1490       1500
aaaatcccaa atcctcgatt tcagagatta tttcagtgtc tgctgcacag agctttacat
      1510       1520       1530       1540       1550       1560
ccccgggagc ctctaccccc aattcagcag catatttgga atatgctgaa tcctcccgct
      1570       1580       1590       1600       1610       1620
gaggtgacaa caaaaagtca gattcctctc tctaaaataa agaccctttt tcctctgatt
      1630       1640       1650       1660       1670       1680
gaagccaaga aaaaggatca agtgactgct caggaaattt tccaagacaa ccatgaagat
      1690       1700       1710       1720       1730       1740
ggacctacag ctaaaaaatt aaagactgag caagggggag cccacttcag cgtctccagt
      1750       1760       1770       1780       1790       1800
ctggctgaag gcagtgtcac ctctgttgga agtgtgaatc ctgctgaaaa cttccgtgtt
      1810       1820       1830       1840       1850       1860
ctagtgaaac agaagaaggc cagctttgag gaagcgagta accagctcat aaatcacatc
      1870       1880       1890       1900       1910       1920
gaacagtttt tggatactaa tgaaacaccg tattttatga agagcataga ctgcatccga
      1930       1940       1950       1960       1970       1980
gccttccggg aagaagccat taagttttca gaagagcagc gctttaacaa cttcctgaaa
      1990       2000       2010       2020       2030       2040
gcccttcaag agaaagtgga aattaaacaa ttaaatcatt tctgggaaat tgttgtccag
      2050       2060       2070       2080       2090       2100
gatggaatta ctctgatcac caaagaggaa gcctctggaa gttctgtcac agctgaggaa
      2110       2120       2130       2140       2150       2160
gccaaaaagt ttctggcccc caaagacaaa ccaagtggag acacagcagc tgtatttgaa
      2170       2180       2190
gaaggtggtg atgtggacga tttattggac atgatatag  

Last modification date: Feb. 6, 2012