Homo sapiens L. (human) [HSA]

FULL NAME: DNA repair protein complementing XP-C cells


DESCRIPTION:
Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity. The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.

MISCELLANEOUS:
Subcellular location: Nucleus. Cytoplasm. Note: Omnipresent in the nucleus and consistently associates with and dissociates from DNA in the absence of DNA damage. Continuously shuttles between the cytoplasm and the nucleus, which is impeded by the presence of NER lesions.


STRUCTURE SIMILARITY:
Belongs to the XPC family.


SUBUNIT STRUCTURE:
Component of the XPC complex composed of XPC, RAD23B and CETN2. Interacts with RAD23A; the interaction is suggesting the existence of a functional equivalent variant XPC complex. Interacts with TDG; the interaction is demonstrated using the XPC:RAD23B dimer. Interacts with SMUG1; the interaction is demonstrated using the XPC:RAD23B dimer. Interacts with DDB2. Interacts with CCNH, GTF2H1 and ERCC3.


POST-TRANSLATIONAL MODIFICATION:
Phosphorylated upon DNA damage, probably by ATM or ATR. Ubiquitinated upon UV irradiation; the ubiquitination requires the UV-DDB complex, appears to be reversible and does not serve as a signal for degradation.


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


RELATED DISEASE(S):
xeroderma pigmentosum, complementation group C (XPC)


Amino acids sequence

        10         20         30         40         50         60
MARKRAAGGE PRGRELRSQK SKAKSKARRE EEEEDAFEDE KPPKKSLLSK VSQGKRKRGC
        70         80         90        100        110        120
SHPGGSADGP AKKKVAKVTV KSENLKVIKD EALSDGDDLR DFPSDLKKAH HLKRGATMNE
       130        140        150        160        170        180
DSNEEEEESE NDWEEAKTRE RSEKIKLEFE TYLRRAMKRF NKGVHEDTHK VHLLCLLANG
       190        200        210        220        230        240
FYRNNICSQP DLHAIGLSII PARFTRVLPR DVDTYYLSNL VKWFIGTFTV NAELSASEQD
       250        260        270        280        290        300
NLQTTLERRF AIYSARDDEE LVHIFLLILR ALQLLTRLVL SLQPIPLKSA TAKGKKPSKE
       310        320        330        340        350        360
RLTADPGGSS ETSSQVLENH TKPKTSKGTK QEETFAKGTC RPSAKGKRNK GGRKKRSKPS
       370        380        390        400        410        420
SSEEDEGPGD KQEKATQRRP HGRERRVASR VSYKEESGSD EAGSGSDFEL SSGEASDPSD
       430        440        450        460        470        480
EDSEPGPPKQ RKAPAPQRTK AGSKSASRTH RGSHRKDPSL PAASSSSSSS KRGKKMCSDG
       490        500        510        520        530        540
EKAEKRSIAG IDQWLEVFCE QEEKWVCVDC VHGVVGQPLT CYKYATKPMT YVVGIDSDGW
       550        560        570        580        590        600
VRDVTQRYDP VWMTVTRKCR VDAEWWAETL RPYQSPFMDR EKKEDLEFQA KHMDQPLPTA
       610        620        630        640        650        660
IGLYKNHPLY ALKRHLLKYE AIYPETAAIL GYCRGEAVYS RDCVHTLHSR DTWLKKARVV
       670        680        690        700        710        720
RLGEVPYKMV KGFSNRARKA RLAEPQLREE NDLGLFGYWQ TEEYQPPVAV DGKVPRNEFG
       730        740        750        760        770        780
NVYLFLPSMM PIGCVQLNLP NLHRVARKLD IDCVQAITGF DFHGGYSHPV TDGYIVCEEF
       790        800        810        820        830        840
KDVLLTAWEN EQAVIERKEK EKKEKRALGN WKLLAKGLLI RERLKRRYGP KSEAAAPHTD
       850        860        870        880        890        900
AGGGLSSDEE EGTSSQAEAA RILAASWPQN REDEEKQKLK GGPKKTKREK KAAASHLFPF

EQL     

Encoded by XPC gene

FULL NAME: xeroderma pigmentosum, complementation group C


OTHER NAME(S):
RAD4
XP3
XPCC


DESCRIPTION:
This gene encodes a component of the nucleotide excision repair (NER) pathway. There are multiple components involved in the NER pathway, including Xeroderma pigmentosum (XP) A-G and V, Cockayne syndrome (CS) A and B, and trichothiodystrophy (TTD) group A, etc. This component, XPC, plays an important role in the early steps of global genome NER, especially in damage recognition, open complex formation, and repair protein complex formation. Mutations in this gene or some other NER components result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]


Nucleic acid sequence

        10         20         30         40         50         60
atggctcgga aacgcgcggc cggcggggag ccgcggggac gcgaactgcg cagccagaaa
        70         80         90        100        110        120
tccaaggcca agagcaaggc ccggcgtgag gaggaggagg aggatgcctt tgaagatgag
       130        140        150        160        170        180
aaacccccaa agaagagcct tctctccaaa gtttcacaag gaaagaggaa aagaggctgc
       190        200        210        220        230        240
agtcatcctg ggggttcagc agatggtcca gcaaaaaaga aagtggccaa ggtgactgtt
       250        260        270        280        290        300
aaatctgaaa acctcaaggt tataaaggat gaagccctca gcgatgggga tgacctcagg
       310        320        330        340        350        360
gactttccaa gtgacctcaa gaaggcacac catctgaaga gaggggctac catgaatgaa
       370        380        390        400        410        420
gacagcaatg aagaagagga agaaagtgaa aatgattggg aagaggcgaa gacaagagaa
       430        440        450        460        470        480
agaagtgaaa agataaaact ggagtttgag acatatcttc ggagggcgat gaaacgtttc
       490        500        510        520        530        540
aataaagggg tccatgagga cacacacaag gttcaccttc tctgcctgct agcaaatggc
       550        560        570        580        590        600
ttctatcgaa ataacatctg cagccagcca gatctgcatg ctattggcct gtccatcatc
       610        620        630        640        650        660
ccagcccgct ttaccagagt gctgcctcga gatgtggaca cctactacct ctcaaacctg
       670        680        690        700        710        720
gtgaagtggt tcattggaac atttacagtt aatgcagaac tttcagccag tgaacaagat
       730        740        750        760        770        780
aacctgcaga ctacattgga aaggagattt gctatttact ctgctcgaga tgatgaggaa
       790        800        810        820        830        840
ttggtccata tattcttact gattctccgg gctctgcagc tcttgacccg gctggtattg
       850        860        870        880        890        900
tctctacagc caattcctct gaagtcagca acagcaaagg gaaagaaacc ttccaaggaa
       910        920        930        940        950        960
agattgactg cggatccagg aggctcctca gaaacttcca gccaagttct agaaaaccac
       970        980        990       1000       1010       1020
accaaaccaa agaccagcaa aggaaccaaa caagaggaaa cctttgctaa gggcacctgc
      1030       1040       1050       1060       1070       1080
aggccaagtg ccaaagggaa gaggaacaag ggaggcagaa agaaacggag caagccctcc
      1090       1100       1110       1120       1130       1140
tccagcgagg aagatgaggg cccaggagac aagcaggaga aggcaaccca gcgacgtccg
      1150       1160       1170       1180       1190       1200
catggccggg agcggcgggt ggcctccagg gtgtcttata aagaggagag tgggagtgat
      1210       1220       1230       1240       1250       1260
gaggctggca gcggctctga ttttgagctc tccagtggag aagcctctga tccctctgat
      1270       1280       1290       1300       1310       1320
gaggattccg aacctggccc tccaaagcag aggaaagccc ccgctcctca gaggacaaag
      1330       1340       1350       1360       1370       1380
gctgggtcca agagtgcctc caggacccat cgtgggagcc atcgtaagga cccaagcttg
      1390       1400       1410       1420       1430       1440
ccagcggcat cctcaagctc ttcaagcagt aaaagaggca agaaaatgtg cagcgatggt
      1450       1460       1470       1480       1490       1500
gagaaggcag aaaaaagaag catagctggt atagaccagt ggctagaggt gttctgtgag
      1510       1520       1530       1540       1550       1560
caggaggaaa agtgggtatg tgtagactgt gtgcacggtg tggtgggcca gcctctgacc
      1570       1580       1590       1600       1610       1620
tgttacaagt acgccaccaa gcccatgacc tatgtggtgg gcattgacag tgacggctgg
      1630       1640       1650       1660       1670       1680
gtccgagatg tcacacagag gtacgaccca gtctggatga cagtgacccg caagtgccgg
      1690       1700       1710       1720       1730       1740
gttgatgctg agtggtgggc cgagaccttg agaccatacc agagcccatt tatggacagg
      1750       1760       1770       1780       1790       1800
gagaagaaag aagacttgga gtttcaggca aaacacatgg accagccttt gcccactgcc
      1810       1820       1830       1840       1850       1860
attggcttat ataagaacca ccctctgtat gccctgaagc ggcatctcct gaaatatgag
      1870       1880       1890       1900       1910       1920
gccatctatc ccgagacagc tgccatcctt gggtattgtc gtggagaagc ggtctactcc
      1930       1940       1950       1960       1970       1980
agggattgtg tgcacactct gcattccagg gacacgtggc tgaagaaagc aagagtggtg
      1990       2000       2010       2020       2030       2040
aggcttggag aagtacccta caagatggtg aaaggctttt ctaaccgtgc tcggaaagcc
      2050       2060       2070       2080       2090       2100
cgacttgctg agccccagct gcgggaagaa aatgacctgg gcctgtttgg ctactggcag
      2110       2120       2130       2140       2150       2160
acagaggagt atcagccccc agtggccgtg gacgggaagg tgccccggaa cgagtttggg
      2170       2180       2190       2200       2210       2220
aatgtgtacc tcttcctgcc cagcatgatg cctattggct gtgtccagct gaacctgccc
      2230       2240       2250       2260       2270       2280
aatctacacc gcgtggcccg caagctggac atcgactgtg tccaggccat cactggcttt
      2290       2300       2310       2320       2330       2340
gatttccatg gcggctactc ccatcccgtg actgatggat acatcgtctg cgaggaattc
      2350       2360       2370       2380       2390       2400
aaagacgtgc tcctgactgc ctgggaaaat gagcaggcag tcattgaaag gaaggagaag
      2410       2420       2430       2440       2450       2460
gagaaaaagg agaagcgggc tctagggaac tggaagttgc tggccaaagg tctgctcatc
      2470       2480       2490       2500       2510       2520
agggagaggc tgaagcgtcg ctacgggccc aagagtgagg cagcagctcc ccacacagat
      2530       2540       2550       2560       2570       2580
gcaggaggtg gactctcttc tgatgaagag gaggggacca gctctcaagc agaagcggcc
      2590       2600       2610       2620       2630       2640
aggatactgg ctgcctcctg gcctcaaaac cgagaagatg aagaaaagca gaagctgaag
      2650       2660       2670       2680       2690       2700
ggtgggccca agaagaccaa aagggaaaag aaagcagcag cttcccacct gttcccattt
      2710
gagcagctgt ga    

Last modification date: Sept. 12, 2012