Homo sapiens L. (human) [HSA]

FULL NAME: DNA excision repair protein ERCC-6


DESCRIPTION:
Essential factor involved in transcription-coupled nucleotide excision repair which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA. It is required for transcription-coupled repair complex formation. It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the at sites of RNA polymerase II-blocking lesions.
The CSB protein is a 168 kDa protein of 1493 amino acids. The CSB protein contains seven helicase-like ATPase motifs and belongs to the SWI2/SNF2 family of proteins usually involved in chromatin remodeling, transcription and DNA repair [Troelstra et al., 1992]. The CSB protein has no functional helicase activity demonstrated in vitro, but possesses a DNA-dependent ATPase activity, which is strongly stimulated by dephosphorylation of CSB upon UV irradiation [Christiansen et al., 2003].
Based on existing data on other SWI2/SNF2 proteins, it can be deduced that the seven helicase-like motifs of CSB are divided into two RecA-like domains that are wrapped around an interdomain cleft involved in DNA-binding and ATP-binding/hydrolysis [Durr et al., 2005]. Helicase motifs I, Ia, II and III are located on the inner surface of domain 1. Helicase motifs III and IV are separated by a linker region. Helicase motifs IV, V and VI are located on domain 2, outside the DNA binding cleft and have been proposed to contact DNA after the ATP-driven conformational change has taken place [Durr et al., 2005; Lewis et al., 2008]. CSB has been implicated in various repair and transcription processes, but the details of these mechanisms are still unclear.

STRUCTURE SIMILARITY:
Contains 1 helicase C-terminal domain.
Contains 1 helicase ATP-binding domain.
Belongs to the SNF2/RAD54 helicase family.


POST-TRANSLATIONAL MODIFICATION:
Ubiquitinated at the C-terminus. Ubiquitination by the CSA complex leads to ERCC6 proteasomal degradation in a UV-dependent manner.
Phosphorylated upon DNA damage, probably by ATM or ATR.


RELATED PATHWAY(S):
nucleotide excision repair (NER)


RELATED DISEASE(S):
Cockayne syndrome, TYPE B (CSB)
cerebro-oculo-facio-skeletal syndrome type 1 (COFS1)
De Sanctis-Cacchione syndrome (DSC)
age-related macular degeneration type 5 (ARMD5)
UV-sensitive syndrome (UVS)
lung cancer


Amino acids sequence

        10         20         30         40         50         60
MPNEGIPHSS QTQEQDCLQS QPVSNNEEMA IKQESGGDGE VEEYLSFRSV GDGLSTSAVG
        70         80         90        100        110        120
CASAAPRRGP ALLHIDRHQI QAVEPSAQAL ELQGLGVDVY DQDVLEQGVL QQVDNAIHEA
       130        140        150        160        170        180
SRASQLVDVE KEYRSVLDDL TSCTTSLRQI NKIIEQLSPQ AATSRDINRK LDSVKRQKYN
       190        200        210        220        230        240
KEQQLKKITA KQKHLQAILG GAEVKIELDH ASLEEDAEPG PSSLGSMLMP VQETAWEELI
       250        260        270        280        290        300
RTGQMTPFGT QIPQKQEKKP RKIMLNEASG FEKYLADQAK LSFERKKQGC NKRAARKAPA
       310        320        330        340        350        360
PVTPPAPVQN KNKPNKKARV LSKKEERLKK HIKKLQKRAL QFQGKVGLPK ARRPWESDMR
       370        380        390        400        410        420
PEAEGDSEGE ESEYFPTEEE EEEEDDEVEG AEADLSGDGT DYELKPLPKG GKRQKKVPVQ
       430        440        450        460        470        480
EIDDDFFPSS GEEAEAASVG EGGGGGRKVG RYRDDGDEDY YKQRLRRWNK LRLQDKEKRL
       490        500        510        520        530        540
KLEDDSEESD AEFDEGFKVP GFLFKKLFKY QQTGVRWLWE LHCQQAGGIL GDEMGLGKTI
       550        560        570        580        590        600
QIIAFLAGLS YSKIRTRGSN YRFEGLGPTV IVCPTTVMHQ WVKEFHTWWP PFRVAILHET
       610        620        630        640        650        660
GSYTHKKEKL IRDVAHCHGI LITSYSYIRL MQDDISRYDW HYVILDEGHK IRNPNAAVTL
       670        680        690        700        710        720
ACKQFRTPHR IILSGSPMQN NLRELWSLFD FIFPGKLGTL PVFMEQFSVP ITMGGYSNAS
       730        740        750        760        770        780
PVQVKTAYKC ACVLRDTINP YLLRRMKSDV KMSLSLPDKN EQVLFCRLTD EQHKVYQNFV
       790        800        810        820        830        840
DSKEVYRILN GEMQIFSGLI ALRKICNHPD LFSGGPKNLK GLPDDELEED QFGYWKRSGK
       850        860        870        880        890        900
MIVVESLLKI WHKQGQRVLL FSQSRQMLDI LEVFLRAQKY TYLKMDGTTT IASRQPLITR
       910        920        930        940        950        960
YNEDTSIFVF LLTTRVGGLG VNLTGANRVV IYDPDWNPST DTQARERAWR IGQKKQVTVY
       970        980        990       1000       1010       1020
RLLTAGTIEE KIYHRQIFKQ FLTNRVLKDP KQRRFFKSND LYELFTLTSP DASQSTETSA
      1030       1040       1050       1060       1070       1080
IFAGTGSDVQ TPKCHLKRRI QPAFGADHDV PKRKKFPASN ISVNDATSSE EKSEAKGAEV
      1090       1100       1110       1120       1130       1140
NAVTSNRSDP LKDDPHMSSN VTSNDRLGEE TNAVSGPEEL SVISGNGECS NSSGTGKTSM
      1150       1160       1170       1180       1190       1200
PSGDESIDEK LGLSYKRERP SQAQTEAFWE NKQMENNFYK HKSKTKHHSV AEEETLEKHL
      1210       1220       1230       1240       1250       1260
RPKQKPKNSK HCRDAKFEGT RIPHLVKKRR YQKQDSENKS EAKEQSNDDY VLEKLFKKSV
      1270       1280       1290       1300       1310       1320
GVHSVMKHDA IMDGASPDYV LVEAEANRVA QDALKALRLS RQRCLGAVSG VPTWTGHRGI
      1330       1340       1350       1360       1370       1380
SGAPAGKKSR FGKKRNSNFS VQHPSSTSPT EKCQDGIMKK EGKDNVPEHF SGRAEDADSS
      1390       1400       1410       1420       1430       1440
SGPLASSSLL AKMRARNHLI LPERLESESG HLQEASALLP TTEHDDLLVE MRNFIAFQAH
      1450       1460       1470       1480       1490
TDGQASTREI LQEFESKLSA SQSCVFRELL RNLCTFHRTS GGEGIWKLKP EYC

Encoded by ERCC6 gene

FULL NAME: excision repair cross-complementing rodent repair deficiency, complementation group 6


OTHER NAME(S):
ARMD5
CKN2
COFS
COFS1
CSB
RAD26


DESCRIPTION:
This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The protein has ATP-stimulated ATPase activity; there are contradictory publications reporting presence or absence of helicase activity. The protein appears to interact with several transcription and excision repair proteins, and may promote complex formation at repair sites. Mutations in this gene result in Cockayne syndrome type B. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgccaaatg agggaatccc ccactcaagt caaactcagg agcaagactg tttacagagt
        70         80         90        100        110        120
caacctgtca gtaataatga agaaatggca atcaagcaag aaagtggtgg tgatggggag
       130        140        150        160        170        180
gtggaggagt acctctcctt tcgttctgtg ggtgacgggc tgtccacctc tgctgtgggg
       190        200        210        220        230        240
tgcgcatcag cagctccgag gagagggcca gccctgctgc acatcgaccg acatcagatc
       250        260        270        280        290        300
caggcagtag agcctagcgc ccaggccctt gagctgcagg gtttgggtgt ggacgtctat
       310        320        330        340        350        360
gaccaggacg tgctggaaca gggagtgctt cagcaggtgg acaatgccat ccatgaggcc
       370        380        390        400        410        420
agccgtgcct cccagctcgt tgacgtggag aaggagtatc ggtcggtcct ggatgacctc
       430        440        450        460        470        480
acgtcatgta cgacatccct aaggcaaatc aataaaatta ttgaacagct tagccctcaa
       490        500        510        520        530        540
gctgccacca gcagagacat caacaggaaa ctagattctg taaaacgaca gaagtataat
       550        560        570        580        590        600
aaggaacaac agctaaaaaa gatcactgca aaacaaaagc atctccaggc catccttgga
       610        620        630        640        650        660
ggagcagagg tgaaaattga actagatcac gccagtctgg aggaggatgc agagccgggg
       670        680        690        700        710        720
ccatccagtc ttggcagcat gctcatgcct gtccaggaga ctgcctggga agagctcatc
       730        740        750        760        770        780
cgcactggcc agatgacacc ttttggtacc cagatccctc agaaacagga gaaaaagccc
       790        800        810        820        830        840
agaaaaatca tgcttaatga agcatcaggc ttcgaaaagt atttggcaga tcaagcaaaa
       850        860        870        880        890        900
ctgtcttttg aaaggaagaa gcaaggttgt aataaaagag cagctagaaa agctccagcc
       910        920        930        940        950        960
ccagtcacgc ctccagcccc agtgcaaaat aaaaacaaac caaacaagaa agccagagtt
       970        980        990       1000       1010       1020
ctgtccaaaa aagaggagcg tttgaaaaag cacatcaaga aactccagaa gagggctttg
      1030       1040       1050       1060       1070       1080
cagttccagg ggaaagtggg attgccaaag gcaaggagac cttgggagtc agacatgagg
      1090       1100       1110       1120       1130       1140
ccagaggcag agggagactc tgagggtgaa gagtctgagt atttccccac agaggaggag
      1150       1160       1170       1180       1190       1200
gaagaggagg aagatgacga ggtggagggg gcagaggcgg acctgtctgg agatggtact
      1210       1220       1230       1240       1250       1260
gactatgagc tgaagcctct gcccaagggc gggaaacggc agaagaaagt gccagtgcag
      1270       1280       1290       1300       1310       1320
gagattgatg atgacttttt cccaagttct ggggaagaag ctgaagctgc ttctgtagga
      1330       1340       1350       1360       1370       1380
gaaggaggag gaggaggtcg gaaagtggga agataccgag atgatggaga tgaagattat
      1390       1400       1410       1420       1430       1440
tataagcagc ggttaaggag atggaataaa ctgagactgc aggacaaaga gaaacgtctg
      1450       1460       1470       1480       1490       1500
aagctggagg acgattctga ggaaagtgat gctgaatttg acgaaggttt taaagtgcca
      1510       1520       1530       1540       1550       1560
ggttttctgt tcaaaaagct ttttaagtac cagcagacag gtgttaggtg gctgtgggaa
      1570       1580       1590       1600       1610       1620
ttgcactgcc agcaggcagg aggaattctg ggagatgaaa tgggattggg caagaccatc
      1630       1640       1650       1660       1670       1680
cagataattg ccttcttggc aggtctgagc tacagcaaga tcaggactcg tggttcaaat
      1690       1700       1710       1720       1730       1740
tacaggtttg aggggttggg tccaactgta attgtctgtc caacaacagt gatgcatcag
      1750       1760       1770       1780       1790       1800
tgggtgaagg aatttcacac gtggtggcct ccgttcagag tggcaattct acatgaaacc
      1810       1820       1830       1840       1850       1860
ggttcctata cccacaaaaa ggagaaacta attcgagatg ttgctcattg tcatggaatt
      1870       1880       1890       1900       1910       1920
ttgatcacat cttactccta cattcgattg atgcaggatg acattagcag gtatgactgg
      1930       1940       1950       1960       1970       1980
cactatgtga tcttggacga aggacacaaa attcgaaatc caaatgctgc tgtcaccctt
      1990       2000       2010       2020       2030       2040
gcttgcaaac agtttcgcac ccctcatcgg atcattctgt ctggctcacc gatgcaaaat
      2050       2060       2070       2080       2090       2100
aacctccgag agctgtggtc gctctttgac ttcatcttcc cgggaaagtt aggcacgttg
      2110       2120       2130       2140       2150       2160
cctgtgttta tggagcagtt ctccgtcccc atcaccatgg ggggatattc aaatgcttcc
      2170       2180       2190       2200       2210       2220
ccagtacagg tcaaaactgc ttacaagtgt gcatgtgtct tacgagatac cataaatcca
      2230       2240       2250       2260       2270       2280
tacctactgc ggagaatgaa gtcagatgtc aagatgagcc tttctttgcc agataaaaat
      2290       2300       2310       2320       2330       2340
gaacaggtct tattttgccg tcttacagat gagcagcata aagtctacca aaatttcgtt
      2350       2360       2370       2380       2390       2400
gattccaaag aagtttacag gattctcaat ggagagatgc agattttctc cggacttata
      2410       2420       2430       2440       2450       2460
gccctaagaa aaatttgcaa ccaccctgat ctcttttctg gaggtcccaa gaatctcaaa
      2470       2480       2490       2500       2510       2520
ggtcttcctg atgatgaact agaagaagat cagtttgggt actggaaacg ttctgggaaa
      2530       2540       2550       2560       2570       2580
atgattgttg ttgagtcttt gttgaaaata tggcacaagc agggtcagcg agtattgctg
      2590       2600       2610       2620       2630       2640
ttttctcagt caaggcagat gctggacata cttgaagtat tccttagagc ccaaaagtat
      2650       2660       2670       2680       2690       2700
acctatctca agatggatgg taccactaca atagcttcaa gacagccact gattacgaga
      2710       2720       2730       2740       2750       2760
tacaatgagg acacatccat atttgtgttt cttctgacca cgcgggtggg cggcttaggt
      2770       2780       2790       2800       2810       2820
gtcaacctga cgggggcaaa cagagttgtc atctatgacc cagactggaa cccaagcacg
      2830       2840       2850       2860       2870       2880
gacacgcagg cccgggagcg agcatggaga ataggccaga agaagcaagt gactgtgtac
      2890       2900       2910       2920       2930       2940
aggctcctga ctgcgggcac cattgaagaa aagatctacc accgacaaat cttcaagcag
      2950       2960       2970       2980       2990       3000
tttttgacaa atagagtgct aaaagaccca aaacaaaggc ggtttttcaa atccaatgat
      3010       3020       3030       3040       3050       3060
ctctatgagc tatttactct gactagtcct gatgcatccc agagcactga aacaagtgca
      3070       3080       3090       3100       3110       3120
atttttgcag gaactggatc agatgttcag acacccaaat gccatctaaa aagaaggatt
      3130       3140       3150       3160       3170       3180
caaccagcct ttggagcaga ccatgatgtt ccaaaacgca agaagttccc tgcttctaac
      3190       3200       3210       3220       3230       3240
atatctgtaa atgatgccac atcatctgaa gagaaatctg aggctaaagg agctgaagta
      3250       3260       3270       3280       3290       3300
aatgcagtaa cttctaatcg aagtgatcct ttgaaagatg accctcacat gagtagtaat
      3310       3320       3330       3340       3350       3360
gtaactagca atgataggct tggagaagag acaaatgcag tatctggacc agaagagttg
      3370       3380       3390       3400       3410       3420
tcagtgatta gtggaaatgg ggaatgttca aattcttcag gaacaggcaa aacttctatg
      3430       3440       3450       3460       3470       3480
ccatctggtg atgaaagcat tgatgaaaag ttaggtcttt cttacaaaag agaaagaccc
      3490       3500       3510       3520       3530       3540
agccaggctc aaacagaagc tttttgggag aataaacaaa tggaaaataa tttttataag
      3550       3560       3570       3580       3590       3600
cacaagtcaa aaacaaaaca tcatagtgtg gcagaagaag agaccctgga gaaacatctg
      3610       3620       3630       3640       3650       3660
agaccaaagc aaaagcctaa gaactctaag cattgcagag acgccaagtt tgaaggaact
      3670       3680       3690       3700       3710       3720
cgaattccac acctggtgaa gaaaaggcgt taccagaagc aagacagtga aaacaagagt
      3730       3740       3750       3760       3770       3780
gaggccaagg aacagagcaa tgacgattat gttttggaaa agcttttcaa aaaatcagtt
      3790       3800       3810       3820       3830       3840
ggcgtgcaca gtgtcatgaa gcacgatgcc atcatggatg gagccagccc agattatgta
      3850       3860       3870       3880       3890       3900
ctggtggagg cagaagccaa ccgagtggcc caggatgccc tgaaagcact gaggctctct
      3910       3920       3930       3940       3950       3960
cgtcagcggt gtctgggagc agtgtctggt gttcccacct ggactggcca cagggggatt
      3970       3980       3990       4000       4010       4020
tctggtgcac cagcaggaaa aaagagtaga tttggtaaga aaaggaattc taacttctct
      4030       4040       4050       4060       4070       4080
gtgcagcatc cttcatcaac atctccaaca gagaagtgcc aggatggcat catgaaaaag
      4090       4100       4110       4120       4130       4140
gagggaaaag ataatgtccc tgagcatttt agtggaagag cagaagatgc agactcttca
      4150       4160       4170       4180       4190       4200
tccgggcccc tcgcttcctc ctcactcttg gctaaaatga gagctagaaa ccacctgatt
      4210       4220       4230       4240       4250       4260
ctgccagagc gtttagaaag tgaaagcggg cacctgcagg aagcttctgc cctgctgccc
      4270       4280       4290       4300       4310       4320
accacagaac acgatgacct tctggtggag atgagaaact tcatcgcttt ccaggcccac
      4330       4340       4350       4360       4370       4380
actgatggcc aggccagcac cagggagata ctgcaggagt ttgaatccaa gttatctgca
      4390       4400       4410       4420       4430       4440
tcacagtctt gtgtcttccg agaactattg agaaatctgt gcactttcca tagaacttct
      4450       4460       4470       4480
ggtggtgaag gaatttggaa actcaagcca gaatactgct aa 

Last modification date: Oct. 2, 2011